Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder.

BACKGROUND: Autism spectrum disorders (ASD) are predominantly neurodevelopmental and largely genetically determined. However, there are human data supporting the idea that fever can improve symptoms in some individuals, but those data are limited and there are almost no data to support this from animal models. We aimed to test the hypothesis that elevated body temperature would improve function in two animal models of ASD. METHODS: We used a 4 h whole-body hyperthermia (WBH) protocol and, separately, systemic inflammation induced by bacterial endotoxin (LPS) at 250 µg/kg, to dissociate temperature and inflammatory elements of fever in two ASD animal models: C58/J and Shank3B- mice. We used one- or two-way ANOVA and t-tests with normally distributed data and Kruskal-Wallis or Mann-Whitney with nonparametric data. Post hoc comparisons were made with a level of significance set at p < 0.05. For correlation analyses, data were adjusted by a linear regression model. RESULTS: Only LPS induced inflammatory signatures in the brain while only WBH produced fever-range hyperthermia. WBH reduced repetitive behaviours and improved social interaction in C58/J mice and significantly reduced compulsive grooming in Shank3B- mice. LPS significantly suppressed most activities over 5-48 h. LIMITATIONS: We show behavioural, cellular and molecular changes, but provide no specific mechanistic explanation for the observed behavioural improvements. CONCLUSIONS: The data are the first, to our knowledge, to demonstrate that elevated body temperature can improve behavioural signs in 2 distinct ASD models. Given the developmental nature of ASD, evidence that symptoms may be improved by environmental perturbations indicates possibilities for improving function in these individuals. Since experimental hyperthermia in patients would carry significant risks, it is now essential to pursue molecular mechanisms through which hyperthermia might bring about the observed benefits.

Testing the effectiveness of a Fatigue and Activity Management Education for Work (FAME-W) intervention for individuals with inflammatory arthritis: Study protocol for a randomized control trial.

BACKGROUND: A work-focused fatigue management intervention, Fatigue and Activity Management Education for Work (FAME-W) programme was developed for individuals with inflammatory arthritis (IA) to manage fatigue in order to maintain demands of their work activities and tasks. This paper presents the protocol for a randomized control trial that will test the effectiveness and acceptability of FAME-W in improving work performance. METHODS: This protocol presents a multisite randomized control trial and mixed methods process evaluation. Eligible participants will be aged 18-65 years with a diagnosis of inflammatory arthritis and will be in paid employment. The primary outcome of the study will be Work Role Functioning (WRF) questionnaire, and the secondary outcomes will be fatigue, mood, health-related quality of life (HRQOL) and pain. Data will be collected immediately pre- and post-intervention and at 3 months of follow-up. The process evaluation will consist of focus groups and individual interviews to explore participants' experiences of FAME-W. Occupational therapists delivering the programme will complete a facilitator log to assess the fidelity and quality of intervention implementations. Facilitators will participate in individual interviews to explore intervention delivery and acceptability. RESULTS: Results will be expected to show that FAME-W will improve work performance by helping participants gain self-management strategies around managing fatigue and other symptoms related to fatigue. CONCLUSION: It is hoped that FAME-W will be an effective and acceptable intervention for individuals with IA in improving work performance by helping them manage their symptoms. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05138445, Registered on 30 November 2021.

Ultrasonography-Guided Intra-Arterial Hyaluronidase Treatment of Vascular Occlusions.

The purpose of this article is to introduce a recommendation for an adjunct approach to the current treatment protocol for vascular occlusion (VO). Current guidelines for treatment of VO do not incorporate the use of ultrasonographic technology. Using bedside ultrasonography has gained recognition as an effective way to map out the vessels of the face to prevent VO. Ultrasonography has also been found to be helpful for treating VO as well as other hyaluronic acid filler-related complications.

How to Start an IV Drip Bar.

The practice of administering intravenous (IV) vitamin infusions is going to increase in the future and medspas are already meeting this demand. Many practices are striving to create an IV drip bar that complements their aesthetic practice. In this article, we provide a blueprint for starting an IV drip bar. We break down the process into several easy steps designed to make any aesthetic practice successful.

Testing the feasibility and acceptability of an online 'Fatigue and Activity Management Education for Work (FAME-W) programme' for individuals with inflammatory arthritis.

INTRODUCTION: Fatigue and Activity Management Education for Work (FAME-W) is a four-week, occupational therapy led programme focussing on fatigue management strategies. FAME-W was designed to be delivered in person; however, due to COVID-19 pandemic it was modified to be an online group-based self-management intervention. The purpose of this study was to test the feasibility and acceptability of the online delivery format of FAME-W. METHODS: This was a mixed methods study. Participants were randomly allocated to intervention or control group. Participants in the intervention group received a four-week online FAME-W. The control group participants received a FAME-W handbook. Participants were required to complete questionnaires on work presenteeism, fatigue, mood, Health Related Quality of Life and pain at baseline, and 3 months post-intervention. Participants in the intervention group attended a focus group immediately following the completion of the programme and the control group participated in individual interviews. RESULTS: Seven of ten individuals recruited participated in the study. Majority of participants had Rheumatoid Arthritis and were working full-time. The mean age of intervention participants was 53 ± 10.4 and 56.5 ± 3.7 for the controls. All participants in the intervention group had 100% attendance, completed all study measures and activities. Participants had positive comments about the programme format, content, and delivery. Improvements were observed in most measures at follow up. CONCLUSION: Results suggest that an online programme to improve work ability was feasible and acceptable to individuals with inflammatory arthritis. The online delivery format was favoured over attending a centre-based programme. The findings support a definitive intervention trial of online FAME-W.

Employee Assistance Programs: A Misunderstood and Underused Resource for Nurses.

As the focus on nurse well-being evolves, an important consideration is the role of an organization's employee assistance program (EAP). Employee assistance programs are historically underused by employees and are not understood in terms of the depth of services and partnerships they can offer. Nurse executives have a key role in maximizing EAP services and utilization as ones who refer staff and who can influence and decide on an EAP partner and related programs and services. This column discusses how EAPs can be a significant tool for nurse leaders in supporting employees.

Design optimisation and characterisation of an amperometric glutamate oxidase-based composite biosensor for neurotransmitter l-glutamic acid.

A polymer/enzyme composite biosensor for monitoring neurochemical glutamate was performance optimised in vitro for sensitivity, selectivity and stability. This first generation Pt/glutamate oxidase-based sensor displayed appropriate sensitivity (90.4 ± 2.0 nA cm-2 µM-1). It also has ideal stability/biocompatibility with no significant decrease in response observed for repeated calibrations, exposure to electron beam sterilisation, or following storage at 4 °C either dry (28 days) or in ex-vivo rodent brain tissue (14 days). Potential non-glutamate contributing signals, generated by extracellular levels of the principal endogenous electroactive interferents, were typically <5% of the basal (10 µM) glutamate response. Changes in molecular oxygen (the natural enzyme mediator) over the normal brain tissue range of 40-80 µM had minimal effect on the glutamate signal for concentrations of 10 and 100 µM (Mean KMO2 = 1.86 ± 0.74 µM, [O2]90% = ca. 15 µM). Additionally, a low µM calculated limit of detection (0.44 ± 0.05) and rapid response time (ca. 1.67 ± 0.06 s), combined with no effect of pH and temperature changes over physiologically relevant ranges (7.2-7.6 and 34-40 °C respectively), collectively suggest that this composite biosensor should reliably detect l-glutamate when used for neurochemical monitoring. Preliminary experiments involving implantation in the striatum of freely moving rats demonstrated stable recording over several weeks, and reliable detection of physiological changes in glutamate in response to behavioural/neuronal activation (locomotor activity and restraint stress).

Development and validation of a real-time microelectrochemical sensor for clinical monitoring of tissue oxygenation/perfusion.

Oxygen is of critical importance to tissue viability and there is increasing demand for its reliable real-time clinical monitoring in order to prevent, diagnose, and treat several pathological disorders, including hypoxia, stroke and reperfusion injury. Herein we report the development and characterisation of a prototype clinical O2 sensor, and its validation in vivo, including proof-of-concept monitoring in patients undergoing surgery for carpal tunnel release. An integrated platinum-based microelectrochemical device was custom designed and controlled using a miniaturised telemetry-operated single channel clinical potentiostat. The in vitro performance of different sensor configurations is presented, with the best sensor design (S2) displaying appropriate linearity (R2 = 0.994) and sensitivity (0.569 ± 0.022 nA µM-1). Pre-clinical validation of S2 was performed in the hind limb muscle of anaesthetised rats; tourniquet application resulted in a significant rapid decrease in signal (90 ± 27%, [ΔO2] ca. 140 ± 18 µM), with a return to baseline within a period of ca. 3 min following tourniquet release. Similar trends were observed in the clinical study; an immediate decrease in signal (39 ± 3%, [ΔO2] ca. 30 ± 20 µM), with basal levels re-established within 2 min of tourniquet release. These results confirm that continuous real-time monitoring of dynamic changes in tissue O2 can serve as an indicator of reperfusion status in patients undergoing carpal tunnel surgery, and suggests the potential usefulness of the developed microelectrochemical sensor for other medical conditions where clinical monitoring of O2 and perfusion is important.

Multicomponent analysis using a confocal Raman microscope.

Measuring the concentration of multiple chemical components in a low-volume aqueous mixture by Raman spectroscopy has received significant interest in the literature. All of the contributions to date focus on the design of optical systems that facilitate the recording of spectra with high signal-to-noise ratio by collecting as many Raman scattered photons as possible. In this study, the confocal Raman microscope setup is investigated for multicomponent analysis. Partial least-squares regression is used to quantify physiologically relevant aqueous mixtures of glucose, lactic acid, and urea. The predicted error is 17.81 mg/dL for glucose, 10.6 mg/dL for lactic acid, and 7.6 mg/dL for urea, although this can be improved with increased acquisition times. A theoretical analysis of the method is proposed, which relates the numerical aperture and the magnification of the microscope objective, as well as the confocal pinhole size, to the performance of the technique.

Use of methadone for the treatment of diabetic neuropathy.

Editor's comment: This is the second Commentary of those that will appear from time to time describing treatments that may not have been validated by appropriate clinical trials but seem to be effective in diabetic patients based on small studies and/or extensive clinical experience. This one describes effective opioid treatment for those diabetic patients failing nonopioid therapies for painful neuropathy.