Flow back along a needle track (backflow) can be a problem during direct infusion, e.g. convection-enhanced delivery (CED), of drugs into soft tissues such as brain. In this study, the effect of ...needle insertion speed on local tissue injury and backflow was evaluated in vivo in the rat brain. Needles were introduced at three insertion speeds (0.2, 2, and 10 mm/s) followed by CED of Evans blue albumin (EBA) tracer. Holes left in tissue slices were used to reconstruct penetration damage. These measurements were also input into a hyperelastic model to estimate radial stress at the needle-tissue interface (pre-stress) before infusion. Fast insertion speeds were found to produce more tissue bleeding and disruption; average hole area at 10 mm/s was 1.87-fold the area at 0.2 mm/s. Hole measurements also differed at two fixation time points after needle retraction, 10 and 25 min, indicating that pre-stresses are influenced by time-dependent tissue swelling. Calculated pre-stresses were compressive (0 to 485 Pa) and varied along the length of the needle with smaller average values within white matter (116 Pa) than gray matter (301 Pa) regions. Average pre-stress at 0.2 mm/s (351.7 Pa) was calculated to be 1.46-fold the value at 10 mm/s. For CED backflow experiments (0.5, 1, and 2 µL/min), measured EBA backflow increased as much as 2.46-fold between 10 and 0.2 mm/s insertion speeds. Thus, insertion rate-dependent damage and changes in pre-stress were found to directly contribute to the extent of backflow, with slower insertion resulting in less damage and improved targeting.
•Friction stress can be evaluated in vivo, in real time, by measuring forces during needle insertion and retraction.•Faster needle insertion produced less friction stress which matches greater track ...damage from our previous study.•Smaller friction stress was measured within white matter regions compared to gray matter regions.
Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in tissue damage which can promote flowback along the needle track and improper targeting. The goal of this study was to evaluate friction stress (calculated from needle insertion force) as a measure of tissue contact and damage during needle insertion for varying insertion speeds.
Forces and surface dimpling during needle insertion were measured in rat brain in vivo. Needle retraction forces were used to calculate friction stresses. These measures were compared to track damage from a previous study. Differences between brain tissues and soft hydrogels were evaluated for varying insertion speeds: 0.2, 2, and 10mm/s.
In brain tissue, average insertion force and surface dimpling increased with increasing insertion speed. Average friction stress along the needle–tissue interface decreased with insertion speed (from 0.58±0.27 to 0.16±0.08kPa). Friction stress varied between brain regions: cortex (0.227±0.27kPa), external capsule (0.222±0.19kPa), and CPu (0.383±0.30kPa). Hydrogels exhibited opposite trends for dimpling and friction stress with insertion speed.
Previously, increasing needle damage with insertion speed has been measured with histological methods. Friction stress appears to decrease with increasing tissue damage and decreasing tissue contact, providing the potential for in vivo and real time evaluation along the needle track.
Force derived friction stress decreased with increasing insertion speed and was smaller within white matter regions. Hydrogels exhibited opposite trends to brain tissue.
The present study tests predictions from the Tripartite Integration Model of Social Influences (TIMSI) concerning processes linking social interactions to social integration into science, technology, ...engineering, and mathematics (STEM) communities and careers. Students from historically overrepresented groups in STEM were followed from their senior year of high school through their senior year in college. Based on TIMSI, we hypothesized that interactions with social influence agents (operationalized as mentor network diversity, faculty mentor support, and research experiences) would promote both short- and long-term integration into STEM via social influence processes (operationalized as science self-efficacy, identity, and internalized community values). Moreover, we examined the previously untested hypothesis of reciprocal influences from early levels of social integration in STEM to future engagement with social influence agents. Results of a series of longitudinal structural equation model-based mediation analyses indicate that, in the short term, higher levels of faculty mentorship support and research engagement, and to a lesser degree more diverse mentor networks in college promote deeper integration into the STEM community through the development of science identity and science community values. Moreover, results indicate that, in the long term, earlier high levels of integration in STEM indirectly influences research engagement through the development of higher science identity. These results extend our understanding of the TIMSI framework and advance our understanding of the reciprocal nature of social influences that draw students into STEM careers.
We present a noninvasive method of photoacoustic tomography (PAT) for imaging cerebral hemodynamics in awake-moving rats. The wearable PAT (wPAT) system has a size of 15 mm in height and 33 mm in ...diameter, and a weight of ~ 8 g (excluding cabling). The wPAT achieved an imaging rate of 3.33 frames/s with a lateral resolution of 243 μm. Animal experiments were designed to show wPAT feasibility for imaging cerebral hemodynamics on awake-moving animals. Results showed that the cerebral oxy-hemoglobin and deoxy-hemoglobin changed significantly in response to hyperoxia; and, after the injection of pentylenetetrazol (PTZ), cerebral blood volume changed faster over time and larger in amplitude for rats in awake-moving state compared with rats under anesthesia. By providing a light-weight, high-resolution technology for in vivo monitoring of cerebral hemodynamics in awake-behaving animals, it will be possible to develop a comprehensive understanding on how activity alters hemodynamics in normal and diseased states.
Waiting times for hospital appointments, treatment and/or surgery have become a major political and health service problem, leading to national maximum waiting times and policies to reduce waiting ...times. Quantitative studies have documented waiting times for various types of surgery and longer waiting times in public vs private hospitals. However, very little qualitative research has explored patient experiences of waiting, how this compares between public and private hospitals, and the implications for trust in hospitals and healthcare professionals. The aim of this paper is to provide a deep understanding of the impact of waiting times on patient trust in public and private hospitals.
A qualitative study in South Australia, including 36 in-depth interviews (18 from public and 18 from private hospitals). Data collection occurred in 2012-13, and data were analysed using pre-coding, followed by conceptual and theoretical categorisation.
Participants differentiated between experiences of 'waiting for' (e.g. for specialist appointments and surgery) and 'waiting in' (e.g. in emergency departments and outpatient clinics) public and private hospitals. Whilst 'waiting for' public hospitals was longer than private hospitals, this was often justified and accepted by public patients (e.g. due to reduced government funding), therefore it did not lead to distrust of public hospitals. Private patients had shorter 'waiting for' hospital services, increasing their trust in private hospitals and distrust of public hospitals. Public patients also recounted many experiences of longer 'waiting in' public hospitals, leading to frustration and anxiety, although they rarely blamed or distrusted the doctors or nurses, instead blaming an underfunded system and over-worked staff. Doctors and nurses were seen to be doing their best, and therefore trustworthy.
Although public patients experienced longer 'waiting for' and 'waiting in' public hospitals, it did not lead to widespread distrust in public hospitals or healthcare professionals. Private patients recounted largely positive stories of reduced 'waiting for' and 'waiting in' private hospitals, and generally distrusted public hospitals. The continuing trust by public patients in the face of negative experiences may be understood as a form of exchange trust norm, in which institutional trust is based on base-level expectations of consistency and minimum standards of care and safety. The institutional trust by private patients may be understood as a form of communal trust norm, whereby trust is based on the additional and higher-level expectations of flexibility, reduced waiting and more time with healthcare professionals.
This invited opinion article reviews current uses and controversies in vernacular and pharmacological cannabidiol use in pediatric neurologic disorders. Since the recent emergence of cannabidiol ...availability to the general public and recent Food and Drug Administration approval, it is important to highlight and expand understanding about CBD mechanism of action, long-term use, safety, and indications in children with neurological disorders.
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, lack of speech, ataxia, EEG abnormalities, and epilepsy. Seizures in individuals with AS are common, ...debilitating, and often drug resistant. Thus, there is an unmet need for better treatment options. Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, has shown antiseizure activity and behavioral benefits in preclinical and clinical studies for some disorders associated with epilepsy, suggesting that the same could be true for AS. Here, we show that acute CBD (100 mg/kg) treatment attenuated hyperthermia- and acoustically induced seizures in a mouse model of AS. However, neither acute CBD nor a 2-week-long course of CBD administered immediately after a kindling protocol could halt the proepileptogenic plasticity observed in AS model mice. CBD had a dose-dependent sedative effect but did not have an impact on motor performance. CBD abrogated the enhanced intracortical local field potential power, including the delta and theta rhythms observed in AS model mice, indicating that CBD administration could also help normalize the EEG deficits observed in individuals with AS. We believe our results provide critical preclinical evidence supporting CBD treatment of seizures and alleviation of EEG abnormalities in AS and will thus help guide the rational development of CBD as a treatment for AS.
Seizure prediction: Methods Carney, Paul R; Myers, Stephen; Geyer, James D
Epilepsy & behavior,
12/2011, Volume:
22, Issue:
Suppl 1
Journal Article
Peer reviewed
Open access
Abstract Epilepsy, one of the most common neurological diseases, affects over 50 million people worldwide. Epilepsy can have a broad spectrum of debilitating medical and social consequences. Although ...antiepileptic drugs have helped treat millions of patients, roughly a third of all patients have seizures that are refractory to pharmacological intervention. The evolution of our understanding of this dynamic disease leads to new treatment possibilities. There is great interest in the development of devices that incorporate algorithms capable of detecting early onset of seizures or even predicting them hours before they occur. The lead time provided by these new technologies will allow for new types of interventional treatment. In the near future, seizures may be detected and aborted before physical manifestations begin. In this chapter we discuss the algorithms that make these devices possible and how they have been implemented to date. We also compare and contrast these measures, and review their individual strengths and weaknesses. Finally, we illustrate how these techniques can be combined in a closed-loop seizure prevention system. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.
We describe a very young child who developed an acute ischemic stroke from a LAO, while affected by COVID-19 and MIS-C, and whom we treated successfully with thrombectomy. We compare his clinical and ...imaging findings with those of the existing case reports, and we explore the multifactorial nature of such a neurovascular complication, particularly in the context of the most recent publications regarding the multifactorial endothelial derangements produced by the illness.
•Cannabidiol significantly reduces median monthly seizure frequency in patients with drug-resistant epilepsy.•Seizure reduction sustained after 24-months of CBD treatment.•Measures of quality of ...life, irritability, hyperactivity, behavior, and sleep showed improvement after CBD treatment.•Limited side effects are caused by the add-on treatment of CBD.
To evaluate the effects of oral pharmacological cannabidiol (CBD) on seizures, side effects, quality of life, behavior, mood, and sleep in children with drug-resistant epilepsy (DRE) during a phase II, prospective, open-label clinical study.
During a phase II expanded access program (EAP) study to evaluate the safety and efficacy of using cannabidiol (CBD) for the long-term treatment of children with drug-resistant epilepsy, secondary outcome measures were also performed, including quality of life (QOLCE), behavior (aberrant behavior checklist ABC), and sleep (children’s sleep habit questionnaire, CSHQ). Participants between the ages of 2 and 16 years of age with drug-resistant epilepsy (n = 35) were included in this EAP. Primary outcomes included change in parent-recorded seizure frequency relative to baseline, as well as the safety and tolerability over the course of 24 months of CBD treatment. Secondary outcomes observed in the first 12 months included changes in child behavior, and cognitive function, and sleep quality.
The median change in overall seizure frequency decreased from baseline (n = 33) by −61.3% (n = 33, Inter Quartile Range (IQR): 43–88%) at month 3, −62.9% at month 6 (n = 29, IQR: 48–92%), −74.7% at month 12 (n = 29, IQR: 64–96%), and finally −83.7% (n = 28, IQR: 68–100%) at the conclusion of 24 months of treatment. Seven (20%) of the 35 patients enrolled withdrew from treatment and observation by month 24: 2 failed inclusion criteria at baseline, 4 due to lack of treatment efficacy, and 1 was lost to follow-up. The 12-month recording of secondary measures revealed a significant improvement in Irritability (-39.4%, n = 28, ABC), Hyperactivity (-45.4%, n = 28, ABC), Cognition in Quality of Life (+14.2%, n = 28, QOLCE), Behavioral function (+14.7%, n = 28, QOLCE), General Health (+14.7%, n = 28, QOLCE), Sleep duration (–33.9%, n = 28, CSHQ), Daytime sleepiness (–23.8%, n = 28, CSHQ), and nocturnal arousals (-36.2%, n = 28, CSHQ).
The results of this phase II open-label study demonstrate that pharmacological CBD significantly reduces seizure frequency, and improves QOL, behavior deficits, and sleep disruption, in children with drug-resistant epilepsy. The results also suggest that CBD is efficacious in controlled seizures over a 2-year period in childhood DRE.
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