PET imaging of Aspergillus infection using Zirconium-89 labeled anti-ß-glucan antibody fragments.

PURPOSE: Invasive fungal diseases, such as pulmonary aspergillosis, are common life-threatening infections in immunocompromised patients and effective treatment is often hampered by delays in timely and specific diagnosis. Fungal-specific molecular imaging ligands can provide non-invasive readouts of deep-seated fungal pathologies. In this study, the utility of antibodies and antibody fragments (Fab) targeting ß-glucans in the fungal cell wall to detect Aspergillus infections was evaluated both in vitro and in preclinical mouse models. METHODS: The binding characteristics of two commercially available ß-glucan antibody clones and their respective antigen-binding Fabs were tested using biolayer interferometry (BLI) assays and immunofluorescence staining. In vivo binding of the Zirconium-89 labeled antibodies/Fabs to fungal pathogens was then evaluated using PET/CT imaging in mouse models of fungal infection, bacterial infection and sterile inflammation. RESULTS: One of the evaluated antibodies (HA-ßG-Ab) and its Fab (HA-ßG-Fab) bound to ß-glucans with high affinity (KD = 0.056 & 21.5 nM respectively). Binding to the fungal cell wall was validated by immunofluorescence staining and in vitro binding assays. ImmunoPET imaging with intact antibodies however showed slow clearance and high background signal as well as nonspecific accumulation in sites of infection/inflammation. Conversely, specific binding of [89Zr]Zr-DFO-HA-ßG-Fab to sites of fungal infection was observed when compared to the isotype control Fab and was significantly higher in fungal infection than in bacterial infection or sterile inflammation. CONCLUSIONS: [89Zr]Zr-DFO-HA-ßG-Fab can be used to detect fungal infections in vivo. Targeting distinct components of the fungal cell wall is a viable approach to developing fungal-specific PET tracers.

The Promise of Molecular Imaging: Focus on Central Nervous System Infections.

Central nervous system (CNS) infections can lead to high mortality and severe morbidity. Diagnosis, monitoring, and assessing response to therapy of CNS infections is particularly challenging with traditional tools, such as microbiology, due to the dangers associated with invasive CNS procedures (ie, biopsy or surgical resection) to obtain tissues. Molecular imaging techniques like positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging have long been used to complement anatomic imaging such as computed tomography (CT) and magnetic resonance imaging (MRI), for in vivo evaluation of disease pathophysiology, progression, and treatment response. In this review, we detail the use of molecular imaging to delineate host-pathogen interactions, elucidate antimicrobial pharmacokinetics, and monitor treatment response. We also discuss the utility of pathogen-specific radiotracers to accurately diagnose CNS infections and strategies to develop radiotracers that would cross the blood-brain barrier.

Imaging Tumor-Targeting Bacteria Using 18F-Fluorodeoxysorbitol Positron Emission Tomography.

BACKGROUND: Microbial-based cancer treatments are an emerging field, with multiple bacterial species evaluated in animal models and some advancing to clinical trials. Noninvasive bacteria-specific imaging approaches can potentially support the development and clinical translation of bacteria-based cancer treatments by assessing the tumor and off-target bacterial colonization. METHODS: 18F-Fluorodeoxysorbitol (18F-FDS) positron emission tomography (PET), a bacteria-specific imaging approach, was used to visualize an attenuated strain of Yersinia enterocolitica, currently in clinical trials as a microbial-based cancer treatment, in murine models of breast cancer. RESULTS: Y. enterocolitica demonstrated excellent 18F-FDS uptake in in vitro assays. Whole-body 18F-FDS PET demonstrated a significantly higher PET signal in tumors with Y. enterocolitica colonization compared to those not colonized, in murine models utilizing direct intratumor or intravenous administration of bacteria, which were confirmed using ex vivo gamma counting. Conversely, 18F-fluorodeoxyglucose (18F-FDG) PET signal was not different in Y. enterocolitica colonized versus uncolonized tumors. CONCLUSIONS: Given that PET is widely used for the management of cancer patients, 18F-FDS PET could be utilized as a complementary approach supporting the development and clinical translation of Y. enterocolitica-based tumor-targeting bacterial therapeutics.

The relationships between multidimensional sleep health and work productivity in individuals with neurological conditions.

Numerous studies have reported the negative impacts of poor sleep on work productivity in the general population. However, despite the known sleep issues that individuals living with neurological conditions experience, no study has explored its impact on their work productivity. Sleep health is a concept that includes multiple domains of sleep, measured with a combination of objective and subjective measures. Therefore, this study aimed to ascertain the associations between sleep health and its domains and work productivity in individuals with neurological conditions. Sleep health domains were determined through actigraphy data collected over 1 week and sleep questionnaires. Work productivity was assessed via the Work Productivity and Activity Impairment Questionnaire. A comparison of sleep health scores between demographic variables was performed using Mann-Whitney U and Kruskal-Wallis tests. Associations between the sleep health domains and work productivity were performed using linear regression models. There were no significant differences in sleep health scores between sex, smoking status, education level, employment status or any work productivity domain. Individuals with non-optimal sleep timing had greater absenteeism (22.99%) than the optimal group. Individuals with non-optimal sleep quality had an increase in presenteeism (30.85%), work productivity loss (26.44%) and activity impairment (25.81%) compared to those in the optimal group. The findings from this study highlight that self-reported sleep quality has the largest impact on work productivity. Improving individuals' sleep quality through triage for potential sleep disorders or improving their sleep hygiene (sleep behaviour and environment) may positively impact work productivity.

Does fatigue influence joint-specific work and ground force production during the first steps of maximal acceleration?

During initial acceleration, the first steps of a maximal-effort (sprint) run often determine success or failure in the capture and evasion of an opponent, and is therefore a vital factor of success in many modern sports. However, accelerative events are commonly performed after having already run considerable distances, and the associated fatigue should impair muscle force production and thus reduce acceleration. Despite this, the effects of running-induced fatigue on our ability to accelerate as well as the running technique used to achieve it have received little attention. We recorded 3-D kinematics and ground reaction forces during the first three steps of the acceleration phase from a standing start before and after performing a high-speed, multi-directional, fatiguing run-walk protocol in well-trained running athletes who were habituated to accelerative sprinting. We found that the athletes were able to maintain their acceleration despite changing running technique, which was associated with use of a more upright posture, longer ground contact time, increased vertical ground reaction impulse, decreased hip flexion and extension velocities, and a shift in peak joint moments, power, and positive work from the hip to the knee joint; no changes were detected in ankle joint function. Thus, a compensatory increase in knee joint function alleviated the reduction in hip flexor-extensor capacity. These acute adaptations may indicate that the hip extensors (gluteal and hamstring muscle groups) were more susceptible to fatigue than the ankle and knee musculature, and may thus be a primary target for interventions promoting fatigue resistance.

Fatigue does not increase limb asymmetry or induce proximal joint power shift in habitual, multi-speed runners.

During prolonged jogging, joint moment and work tend to decrease in the distal (ankle) joint but increase at proximal (hip/knee) joints as performance fatigue manifests, and such adaptations might be expected to occur in sprinting. Fatigue is also thought to increase inter-limb asymmetries, which is speculated to influence injury risk. However, the effects of fatigue on sprint running gait have been incompletely studied, so these hypotheses remain untested. Using statistical parametric mapping, we compared 3-D kinematics and ground reaction force production between the dominant (DL) and non-dominant (NDL) legs of 13 soccer players during both non-fatigued and fatigued sprint running. Contrary to the tested hypotheses, relative between-leg differences were greater in non-fatigued than fatigued sprinting. DL generated higher propulsive impulse due to increased ankle work, while NDL exhibited greater vertical impulse, potentially due to greater hip flexion prior to downward foot acceleration. Whilst few changes were detected in DL once fatigued, NDL shifted towards greater horizontal force production, largely resulting from an increase in plantar flexion (distal-joint) moments and power. After fatiguing running, inter-limb asymmetry was reduced and no distal-to-proximal shift in joint work was detected. These adaptations may attenuate decreases in running speed whilst minimising injury risk.

Profiling Social Cognition in Premanifest Huntington's Disease.

OBJECTIVE: Discrepancies exist in reports of social cognition deficits in individuals with premanifest Huntington's disease (HD); however, the reason for this variability has not been investigated. The aims of this study were to (1) evaluate group- and individual-level social cognitive performance and (2) examine intra-individual variability (dispersion) across social cognitive domains in individuals with premanifest HD. METHOD: Theory of mind (ToM), social perception, empathy, and social connectedness were evaluated in 35 individuals with premanifest HD and 29 healthy controls. Cut-off values beneath the median and 1.5 × the interquartile range below the 25th percentile (P25 - 1.5 × IQR) of healthy controls for each variable were established for a profiling method. Dispersion between social cognitive domains was also calculated. RESULTS: Compared to healthy controls, individuals with premanifest HD performed worse on all social cognitive domains except empathy. Application of the profiling method revealed a large proportion of people with premanifest HD fell below healthy control median values across ToM (>80%), social perception (>57%), empathy (>54%), and social behaviour (>40%), with a percentage of these individuals displaying more pronounced impairments in empathy (20%) and ToM (22%). Social cognition dispersion did not differ between groups. No significant correlations were found between social cognitive domains and mood, sleep, and neurocognitive outcomes. CONCLUSIONS: Significant group-level social cognition deficits were observed in the premanifest HD cohort. However, our profiling method showed that only a small percentage of these individuals experienced marked difficulties in social cognition, indicating the importance of individual-level assessments, particularly regarding future personalised treatments.

Exploring the brain-body composition relationship in Huntington's disease.

OBJECTIVE: Changes in body composition are a common feature of Huntington's disease (HD) and are associated with disease progression. However, whether these changes in body composition are associated with degeneration of the striatum is unknown. This study aimed to explore the associations between body composition metrics and striatal brain volume in individuals with premanifest HD and healthy controls. METHODS: Twenty-one individuals with premanifest HD and 22 healthy controls participated in this cross-sectional study. Body composition metrics were measured via dual-energy X-ray absorptiometry. Structural magnetic resonance imaging of subcortical structures of the brain was performed to evaluate striatal volume. RESULTS: There were no significant differences in body composition metrics between the premanifest HD and healthy controls group. Striatal volume was significantly reduced in individuals with premanifest HD compared to healthy controls. A significant association between bone mineral density (BMD) and right putamen volume was also observed in individuals with premanifest HD. CONCLUSION: These findings show striatal degeneration is evident during the premanifest stages of HD and associated with BMD. Additional longitudinal studies are nevertheless needed to confirm these findings.

Peripheral Immunotype Correlates with Minimal Residual Disease Status and Is Modulated by Immunomodulatory Drugs in Multiple Myeloma.

Data indicate reversal of immune dysfunction with active treatment; however, the precise contribution of specific immune effector and immune suppressor components to achieve a minimal residual disease (MRD) state and immunomodulatory drug-mediated immunomodulatory effects in multiple myeloma (MM) patients remains poorly understood. In this prospective proof-of-principle study we sought to determine the dynamic alterations in natural killer (NK), NK-T, and T cells, including maturation and activating/inhibitory repertoire associated with MRDpos versus MRDneg status after autologous stem cell transplantation (ASCT) and during lenalidomide-based maintenance therapy. Of the 46MM patients enrolled, 36 had bone marrow MRD assessment 60+ days post-ASCT, 30 had longitudinal blood immunotyping during maintenance (pretherapy and after cycles 1, 3, and 6), and 20 had both MRD assessment and longitudinal immunotyping. Multicolor flow cytometry was used for MRD and immunotyping. Although the absolute number of NK cells was significantly lower in patients with MRDpos response, phenotypically NK cells in these patients displayed higher expression of activating receptors KIRDS4 and decreased expression of inhibitory molecules NKG2A compared with the MRDneg group. Furthermore, we observed significantly lower frequencies of T cells displaying KIR3DL1 in MRDpos versus MRDneg patients. Longitudinal immunotyping during lenalidomide maintenance showed loss of mature NK effector function, augmentation of NK-T effector function, and acquisition of PD1 independent anergic state. Our findings also suggest skewing of T cells toward an exhausted state during the maintenance phase in MRDpos patients. Put together, these observations provide a distinctive signature for MRDneg and MRDpos groups. These data support exploration of immune profiling in prospective clinical trials according to MRD-defined responses to identify patients that may benefit from maintenance intensification/modification or maintenance withdrawal.

The multidimensional sleep health of individuals with multiple sclerosis and Huntington's disease and healthy controls.

STUDY OBJECTIVES: Sleep issues are common for people with neurodegenerative conditions, yet research has focused on specific aspects of sleep. While important, a more holistic approach to investigating sleep, termed "sleep health," considers sleep's positive and negative aspects. Current studies exploring sleep health have lacked a control group for reference. For the first time, this study investigated the sleep health of people living with multiple sclerosis and Huntington's disease (HD) and compared it with a community sample. METHODS: 111 people, including 43 with multiple sclerosis, 19 with HD, and 49 from a community sample, participated in this study. The data, including actigraphy, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale, were collected as part of ongoing research studies. Seven sleep health domains were determined from the collected data, and a composite sleep health score was developed. Analysis of variance and independent t tests were performed to identify population and sex differences. RESULTS: The HD group had higher sleep regularity and lower sleep rhythmicity than the multiple sclerosis and community sample groups. The HD group had significantly less sleep duration than the multiple sclerosis group. No significant differences between the groups were observed in the sleep health composite score. Males had significantly higher sleep regularity within the HD group but significantly lower sleepiness scores in the community sample. CONCLUSIONS: These findings indicate that people with HD may experience greater variance in their wake times, therefore decreasing the consistency of being awake or asleep 24 hours apart. Understanding the mechanisms for this should be explored in people with HD. CITATION: Turner M, Griffiths M, Laws M, Vial S, Bartlett D, Cruickshank T. The multidimensional sleep health of individuals with multiple sclerosis and Huntington's disease and healthy controls. J Clin Sleep Med. 2024;20(6):967-972.

Associations between Sleep Quality and Serum Levels of Neurofilament Light in Individuals with Premanifest Huntington Disease.

Objectives To evaluate the associations between sleep quality and serum levels of neurofilament light (NfL) protein in individuals with premanifest Huntington disease (HD). Materials and Methods We recruited 28 individuals with premanifest HD from a pre-existing database (of the Huntington's Environmental Research Optimisation Scheme, HEROs). The participants filled out the Pittsburgh Sleep Quality Index (PSQI), a subjective measure of sleep quality, and blood was collected via routine venepuncture to measure peripheral NfL levels. Results The PSQI scores (median: 5.0; interquartile range: 4.0-7.5) indicated poor sleep quality. General linear modelling revealed no significant ( p = 0.242) association between PSQI scores and NfL levels. No significant differences were found between individuals with good and poor sleep quality for any demographic variable collected. Discussion Contrary to studies on other neurological conditions, there was no association between sleep quality and NfL levels in individuals with premanifest HD. This was unexpected, given the influence of environmental factors (such as social network size) on neurodegeneration in individuals with premanifest HD.

FIGHT-PD: A feasibility study of periodized boxing training for Parkinson disease.

BACKGROUND: Boxing training has become a popular form of exercise for people with Parkinson disease (PD). There is a dearth of high-quality feasibility, safety, and efficacy data on boxing training for PD. Feasibility of Instituting Graduated High-intensity Training (FIGHT-PD) aimed to examine these features in a periodized boxing training program featuring high-intensity physical and cognitive demands. OBJECTIVE: To conduct a feasibility study, aiming to address deficiencies in the current knowledge base and to provide data for future studies. DESIGN: Single-arm, open-label feasibility. SETTING: University department and medical research institute. PARTICIPANTS: Ten people with early stage PD without contraindications to intense exercise, identified from a database of participants interested in boxing training. INTERVENTIONS: A 15-week exercise program with three 1-hour sessions per week, with each session including warmup and then rounds of noncontact boxing using a training device. Three distinct blocks of 5 weeks including active rest. Boxers Development: focus on training technique Boxers Cardio: increasing intensity, including high-intensity interval training Boxers Brain: focus on cognitively challenging dual task training MAIN OUTCOME MEASURES: Process, resource, and management measures including recruitment and retention rates, timelines and costs, and compliance with prescribed exercise targets. Clinical outcomes were safety (adverse events), training intensity (using heart rate and perceived exertion monitoring), tolerability (pain, fatigue, and sleep scores), and pre- and postprogram Unified Parkinson Disease Rating Scale (UPDRS-III). RESULTS: Among 10 participants from a pool of 82 (recruitment rate = 12%), there were no withdrawals; 348/360 workouts were completed (adherence = 97.7%); 4/348 (1.1%) workouts were missed due to minor injury. Nine of 10 participants showed improvement in UPDRS motor score. CONCLUSIONS: FIGHT-PD provides a depth of feasibility and safety data, methodological detail, and preliminary results that is not described elsewhere and could provide a useful basis for future studies of boxing training for PD.

Sleep health of Australian community tennis players during the COVID-19 lockdown.

Background: Poorer sleep health outcomes have been documented in the general population during the COVID-19 outbreak. However, the impact of the COVID-19 outbreak on sleep health outcomes in specific population groups, including the sporting community, has not been extensively investigated. This study evaluated sleep health outcomes and their relationship with lifestyle behaviours during the initial COVID-19 lockdown period in Australian community tennis players. Methods: This cross-sectional study evaluated sleep health outcomes and lifestyle behaviours using an online survey. The survey was disseminated online between the 24th of April and the 6th of June 2020 and comprised the Sleep Health Index, Sleep Satisfaction Tool and questions regarding weekly hours of tennis play, general physical activity, training location and alcohol consumption. Two-hundred and eighty-five individuals completed the survey. Results: Compared to normative data, respondents displayed positive sleep health values during the initial COVID-19 lockdown period, with median values (IQR) of 85.3 (73.4, 91.7) and 64.8 (54.4, 73.4) for the Sleep Health Index and Sleep Satisfaction Tool, respectively. Sleep health outcomes were not significantly correlated (p > 0.05) with tennis play (Tb = 0.054-0.077), physical activity (Tb = -0.008 to 0.036), training location (Tb = -0.012 to -0.005) or alcohol consumption (Tb = -0.079 to -0.018). Conclusion: Positive sleep health values were observed in Australian community-level tennis players during the initial COVID-19 pandemic. Sleep health values were not associated with lifestyle behaviours. Other unexplored factors may have influenced sleep health outcomes, including personal finances and socialisation, however these factors need to be investigated in future studies.

Effect of physical activity during COVID-19 on the sleep health of community-level athletes in Australia.

The COVID-19 outbreak presents a serious health challenges, with Australia enforcing tight restrictions, impacting sporting activities and sleep health of many Australians. Routine lifestyle patterns (physical activity and employment) are important to maintaining overall sleep health. Current literature indicates COVID-19 pandemic negatively affected the employment status and sport engagement. The aim of this study was to explore the effect of physical activity during COVID-19 on sleep health, and its association with employment and sport engagement of community-level athletes throughout Australia. Participants self-reported sleep health prior to COVID-19 (pre-sleep) and over the month prior to data collection (during-sleep) using the validated 5-item Satisfaction Alertness Timing Efficiency and Duration questionnaire (SATED). Wilcoxon Signed Rank Test assessed the difference in pre- and during perceived sleep health scores. A generalized linear model was used to assess the impact of sporting and demographic factors on a community athlete's change in perceived sleep health score. A total of 139 community-level Australian athletes responded. The majority of participants were aged 18-30 and engaged in full-time employment prior to COVID-19 (n = 82, 54%). Eight percent of participants were unemployed prior to the COVID-19 pandemic (n = 12, 8%). Our findings show that sleep health values were higher during COVID-19, with 91.4% of respondents able to maintain some form of physical activity during the pandemic. Together, our results show better sleep health scores reported by the respondents who maintained or lost employment and maintained sporting engagements during the pandemic.

Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are limited therapeutic options for the prevention and treatment of SARS-CoV-2 infections. We evaluated the antiviral activity of sulforaphane (SFN), the principal biologically active phytochemical derived from glucoraphanin, the naturally occurring precursor present in high concentrations in cruciferous vegetables. SFN inhibited in vitro replication of six strains of SARS-CoV-2, including Delta and Omicron, as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN should be explored as a potential agent for the prevention or treatment of coronavirus infections.

Influence of the COVID-19 Pandemic on Mood and Training in Australian Community Tennis Players.

The COVID-19 outbreak has led to the implementation of strict restrictions in Australia, which have severely impacted sporting activities. Tennis is played by 6.2% of the population within the Oceania region, and is a valuable sport for maintaining social, mental, and physical health. Current literature indicates the COVID-19 pandemic has negatively affected the mental health of Australian residents. The aim of this study was to investigate changes in training and match play due to the outbreak, and its effects on emotional well-being of Australian senior tennis players. Additionally, explore any differences between middle aged (41-60 years) and senior (61 years and over) Australian tennis players. An online survey was used to assess training and match play habits, as well as ascertain the emotional well-being of tennis players. The survey was active from 24th April 2020 until 6th June 2020. Participants were adult (41+ years) tennis players from Australia. Wilcoxon signed rank tests were performed to check for differences in training hours and tennis matches played. Mann-Whitney U tests were used to assess the difference in Brief Emotional Experience Scale (BEES) scores, employment status as well as the training hours and tennis matches played between the two age groups. A Kendall's Tau B correlation test was performed to assess the associations of training, match play and demographic characteristics with BEES scores. Kruskal-Wallis tests assessed differences in BEES scores between participants of differing match play formats, tennis experience and cessation of tennis training time periods. There were 245 respondents who met our inclusion criteria. Tennis training hours along with the tennis matches played significantly decreased during COVID-19 compared to pre-COVID-19, 85.09 and 88.48%, respectively. No significant (p > 0.05) differences were observed between age groups for any of the training modality hours, nor was there any significant difference in number of tennis matches played. The participants average BEES score was 0.99 ± 1.27, indicating that respondents had a positive emotional well-being during the COVID-19 pandemic. The emotional well-being of the senior group was significantly (P = 0.002) higher than the middle aged group. Together, our results show that training and tennis match play decreased during the COVID-19 pandemic, however the emotional well-being of senior tennis players in Australia appeared to not be negatively affected.

Torque variability of the plantar flexors in people with Huntington's disease.

BACKGROUND: Torque steadiness can be impaired in people with Huntington's disease (HD) and worsen with disease advancement. However, existing studies have several methodological oversights. Studies have used absolute torque targets, which do not account for differences in maximal torque capacity between people. Furthermore, despite its known influence on torque steadiness, previous studies in HD have not controlled for visual feedback. This study evaluated torque variability at relative intensities with and without visual feedback between people with prodromal HD and healthy controls. METHODS: Twenty-four people with prodromal HD and twenty-seven age- and sex-matched healthy controls were recruited for this study. Torque variability was evaluated, with and without visual feedback, in the right plantar flexors at 10% and 30% of each participant's maximum voluntary isometric contraction (MVIC). Measures of disease burden included the CAG age product, diagnostic confidence level and Unified Huntington's Disease Rating Scale - Total Motor Score. RESULTS: Significant differences in torque variability were observed, though not in overall MVIC, between people with prodromal HD and healthy controls. Significantly higher torque fluctuations were observed for both groups when visual feedback was removed. No associations were observed between torque variability and disease burden in people with prodromal HD. Torque variability measurements showed higher reliability in healthy controls. CONCLUSIONS: People with prodromal HD exhibited greater torque variability than healthy controls. Torque variability worsened for both groups when visual feedback was removed. These findings support further investigation into the utilisation of torque variability measurements as markers of disease progression in people with prodromal HD.

A Survey to Evaluate the Association of COVID-19 Restrictions on Perceived Mood and Coping in Australian Community Level Athletes.

Highlights: No differences in coping or well-being in Australian community athletes based on the level of support received during COVID-19 restrictions.Community level athletes had better coping when a training program was provided.No difference between individual or team community athletes for well-being or coping scores. Australian community level athletes faced unprecedented changes to their training and competition options as the global COVID-19 pandemic took a stronghold. This disruption was predicted to have a negative impact on emotional well-being as communities braced through periods of social isolation and physical distancing requirements. This study provides an Australian perspective on the emotional well-being of community level athletes and the extent to which they coped during the COVID-19 pandemic. Emotional well-being and coping were measured using the Brief Emotional Experience Scale and the 28-item Brief Cope Scale. Both instruments were administered along with other questions pertaining to participant demographics and training status via an online survey between April and June 2020. The survey was disseminated to community athletes through word-of-mouth and social media platforms. No significant differences in emotional well-being were observed between athlete groups as a result of COVID-19 and its associated restrictions. Coping scores also appeared to be preserved in Australian community athletes, which contrasts the impact expected as a result of the COVID-19 pandemic. While tentative, the observed preservation in coping may have buffered potential declines in emotional well-being, which has been documented in professional and semi-professional athletes and the general population. These unexpected findings and tentative suppositions warrant further investigation and highlight the importance of conducting a country- or region-specific approach to examining the impact of COVID-19 on community athletes, as responses to COVID-19 are undoubtedly not consistent throughout the world.

Vapor exposure to Δ9-tetrahydrocannabinol (THC) slows locomotion of the Maine lobster (Homarus americanus).

RATIONALE: Despite a long history of use in synaptic physiology, the lobster has been a neglected model for behavioral pharmacology. A restaurateur proposed that exposing lobster to cannabis smoke reduces anxiety and pain during the cooking process. It is unknown if lobster gill respiration in air would result in significant Δ9-tetrahydrocannabinol (THC) uptake and whether this would have any detectable behavioral effects. OBJECTIVE: The primary goal was to determine tissue THC levels in the lobster after exposure to THC vapor. Secondary goals were to determine if THC vapor altered locomotor behavior or nociception. METHODS: Tissue samples were collected (including muscle, brain and hemolymph) from Homarus americanus (N = 3 per group) following 30 or 60 min of exposure to vapor generated by an e-cigarette device using THC (100 mg/mL in a propylene glycol vehicle). Separate experiments assessed locomotor behavior and hot water nociceptive responses following THC vapor exposure. RESULTS: THC vapor produced duration-related THC levels in all tissues examined. Locomotor activity was decreased (distance, speed, time-mobile) by 30 min inhalation of THC. Lobsters exhibit a temperature-dependent withdrawal response to immersion of tail, antennae or claws in warm water; this is novel evidence of thermal nociception for this species. THC exposure for 60 min had only marginal effect on nociception under the conditions assessed. CONCLUSIONS: Vapor exposure of lobsters, using an e-cigarette based model, produces dose-dependent THC levels in all tissues and reduces locomotor activity. Hot water nociception was temperature dependent, but only minimal anti-nociceptive effect of THC exposure was confirmed.

Chemiluminescent Protease Probe for Rapid, Sensitive, and Inexpensive Detection of Live Mycobacterium tuberculosis.

Tuberculosis (TB) is a top-ten cause of death worldwide. Successful treatment is often limited by insufficient diagnostic capabilities, especially at the point of care in low-resource settings. The ideal diagnostic must be fast, be cheap, and require minimal clinical resources while providing high sensitivity, selectivity, and the ability to differentiate live from dead bacteria. We describe here the development of a fast, luminescent, and affordable sensor of Hip1 (FLASH) for detecting and monitoring drug susceptibility of Mycobacterium tuberculosis (Mtb). FLASH is a selective chemiluminescent substrate for the Mtb protease Hip1 that, when processed, produces visible light that can be measured with a high signal-to-noise ratio using inexpensive sensors. FLASH is sensitive to fmol of recombinant Hip1 enzyme in vitro and can detect as few as thousands of Mtb cells in culture or in human sputum samples within minutes. The probe is highly selective for Mtb compared to other nontuberculous mycobacteria and can distinguish live from dead cells. Importantly, FLASH can be used to measure antibiotic killing of Mtb in culture with greatly accelerated timelines compared to traditional protocols. Overall, FLASH has the potential to enhance both TB diagnostics and drug resistance monitoring in resource-limited settings.