The Ighmbp2D564N mouse model is the first SMARD1 model to demonstrate respiratory defects.

Spinal muscular atrophy with respiratory distress type I (SMARD1) is a neurodegenerative disease defined by respiratory distress, muscle atrophy and sensory and autonomic nervous system defects. SMARD1 is a result of mutations within the IGHMBP2 gene. We have generated six Ighmbp2 mouse models based on patient-derived mutations that result in SMARD1 and/or Charcot-Marie Tooth Type 2 (CMT2S). Here we describe the characterization of one of these models, Ighmbp2D564N (human D565N). The Ighmbp2D564N/D564N mouse model mimics important aspects of the SMARD1 disease phenotype, including motor neuron degeneration and muscle atrophy. Ighmbp2D564N/D564N is the first SMARD1 mouse model to demonstrate respiratory defects based on quantified plethysmography analyses. SMARD1 disease phenotypes, including the respiratory defects, are significantly diminished by intracerebroventricular (ICV) injection of ssAAV9-IGHMBP2 and the extent of phenotypic restoration is dose-dependent. Collectively, this model provides important biological insight into SMARD1 disease development.

Long-term effects of a coalmine fire on hospital and ambulance use: An interrupted time series study.

BACKGROUND: In 2014, the Hazelwood coalmine fire in regional Victoria, Australia shrouded nearby communities in smoke for six weeks. Prior investigations identified substantial adverse effects, including increases in the use of health services. In this study, we examined the effects on hospital and ambulance use in the eight years following the fire. METHODS: Using Victorian hospital (Jan 2009-Jun 2022) and ambulance (Jan 2013-Dec 2021) data, we conducted an interrupted time series of changes to the rate of hospital admissions, emergency presentations, and ambulance attendances. A categorical exposure model compared two locations, most-exposed Morwell and less-exposed Latrobe Valley, to the rest of regional Victoria. A continuous exposure model used spatial estimates of fire-related PM2.5. Analyses were stratified by sex, age group (<65/65+ years), and condition (cardiovascular, respiratory, mental health, injury). RESULTS: There were small but significant increases in overall hospital admissions and emergency presentations across all analyses, but little evidence of change in overall ambulance attendances. Effects varied considerably by condition, with the biggest relative increases observed among hospital admissions for mental health conditions and injuries. While cardiovascular-related hospital admissions and emergency presentations increased post-fire, ambulance attendances decreased. CONCLUSIONS: Our findings suggest the Hazelwood coalmine fire likely increased hospital usage. However, it is unclear whether this was due to the direct effects of smoke exposure on health, or the disruptive socioeconomic and behavioural impacts of an environmental disaster that affected how communities engaged with various health services.

Does diet quality moderate the long-term effects of discrete but extreme PM2.5 exposure on respiratory symptoms? A study of the Hazelwood coalmine fire.

In 2014, a fire at an open cut coalmine in regional Victoria, Australia burned for 6 weeks. Residents of the nearby town of Morwell were exposed to smoke, which included high levels of fine particulate matter (PM2.5). We investigated whether the long-term effects of PM2.5 on respiratory health were moderated by diet quality. A cross-sectional analysis was conducted of data collected 8.5 years after the mine fire from 282 residents of Morwell and 166 residents from the nearby unexposed town of Sale. Primary outcomes were respiratory symptoms. Exposure was coalmine fire-related PM2.5 and diet quality was assessed as Australian Recommended Food Score (ARFS) derived using the Australian Eating Survey (AES). The moderating effect of diet quality on respiratory outcomes associated with PM2.5 was assessed using logistic regression models, adjusting for potential confounders. Diet quality was poor in this sample, with 60% in the lowest category of overall diet quality. Overall diet quality and fruit and vegetable quality significantly attenuated the association between PM2.5 and prevalence of chronic cough and phlegm. Sauce/condiment intake was associated with a greater effect of PM2.5 on COPD prevalence. No other moderating effects were significant. The moderating effects of overall diet quality and vegetable and fruit intake aligned with a priori hypotheses, suggesting potential protective benefits. While more evidence is needed to confirm these findings, improving diets, especially fruit and vegetable intake, may provide some protection against the effects of smoke exposure from fire events.

Long-term effects of extreme smoke exposure on COVID-19: A cohort study.

BACKGROUND: In 2014, the Hazelwood coalmine fire shrouded the regional Australian town of Morwell in smoke and ash for 6 weeks. One of the fire's by-products, PM2.5 , is associated with an increased risk of COVID-19 and severe disease. However, it is unclear whether the effect persisted for years after exposure. In this study, we surveyed a cohort established prior to the pandemic to determine whether PM2.5 from the coalmine fire increased long-term vulnerability to COVID-19 and severe disease. METHODS: From August to December 2022, 612 members of the Hazelwood Health Study's adult cohort, established in 2016/17, participated in a follow-up survey that included standardized items to capture COVID-19 cases, as well as questions about hospitalization and vaccinations. Associations were evaluated in crude and adjusted logistic regression models. RESULTS: A total of 268 (44%) participants self-reported or met symptom criteria for having had COVID-19 at least once. All models found a positive association, with odds of COVID-19 increasing by between 4% and 30% for a 10 µg/m3 increase in coalmine fire-related PM2.5 exposure. However, the association was significant in only 2 of the 18 models. There were insufficient hospitalizations to examine severity (n = 7; 1%). CONCLUSION: The findings are inconclusive on the effect of coalmine fire-related PM2.5 exposure on long-term vulnerability to COVID-19. Given the positive association that was robust to modelling variations as well as evidence for a causal mechanism, it would be prudent to treat PM2.5 from fire events as a long-term risk factor until more evidence accumulates.

Association between PM2.5 from a coal mine fire and FeNO concentration 7.5 years later.

BACKGROUND AND AIM: There are few long-term studies of respiratory health effects of landscape fires, despite increasing frequency and intensity due to climate change. We investigated the association between exposure to coal mine fire PM2.5 and fractional exhaled nitric oxide (FeNO) concentration 7.5 years later. METHODS: Adult residents of Morwell, who were exposed to the 2014 Hazelwood mine fire over 6 weeks, and unexposed residents of Sale, participated in the Hazelwood Health Study Respiratory Stream in 2021, including measurements of FeNO concentration, a marker of eosinophilic airway inflammation. Individual exposure to coal mine fire PM2.5 was modelled and mapped to time-location diaries. The effect of exposure to PM2.5 on log-transformed FeNO in exhaled breath was investigated using multivariate linear regression models in the entire sample and stratified by potentially vulnerable subgroups. RESULTS: A total of 326 adults (mean age: 57 years) had FeNO measured. The median FeNO level (interquartile range [IQR]) was 17.5 [15.0] ppb, and individual daily exposure to coal mine fire PM2.5 was 7.2 [13.8] µg/m3. We did not identify evidence of association between coal mine fire PM2.5 exposure and FeNO in the general adult sample, nor in various potentially vulnerable subgroups. The point estimates were consistently close to zero in the total sample and subgroups. CONCLUSION: Despite previous short-term impacts on FeNO and respiratory health outcomes in the medium term, we found no evidence that PM2.5 from the Hazelwood coal mine fire was associated with any long-term impact on eosinophilic airway inflammation measured by FeNO levels.

Vocational functioning in young people accessing services for first-episode psychosis and ultra-high risk of psychosis: A longitudinal naturalistic cohort study.

AIMS: Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment. METHODS: This is a naturalistic sample of young people aged 12-25 with FEP (n = 1574) and UHR (n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time. RESULTS: On entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment. CONCLUSION: While there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care.

Long-term impact of the 2014 Hazelwood coal mine fire on emergency department presentations in Australia.

BACKGROUND: In 2014, wildfires ignited a coal mine in Australia, burning for 6 weeks, releasing large amounts of fine particulate matter ≤2.5 µm in diameter (PM2.5). We investigated the association between individual PM2.5 exposure and emergency department presentations (EDPs) within 5 years post-fire. METHODS: Survey and exposure data for 2725 residents from an exposed and unexposed town were linked with ED administrative data from 2009 to 2019. The association between individual PM2.5 and EDPs was assessed using recurrent survival analysis. RESULTS: A 10 µg/m3 increase in PM2.5 was associated with a 10% increase in respiratory EDPs (HR = 1.10; 95%CI:1.00-1.22) over 5 years post-fire. Increased risks of EDPs for ischaemic heart disease (HR = 1.39; 95%CI:1.12-1.73), atherothrombotic disease (HR = 1.27; 95%CI:1.08-1.50), and cardiovascular disease (HR = 1.10, 95%CI:0.99-1.22) were evident within 2.5 years. CONCLUSION: PM2.5 exposure from a 6-week mine fire increased the 5-year risk of respiratory conditions. An increased risk of CVD within 2.5 years post-fire subsided after this time.

Somatic symptoms, psychological distress and trauma after disasters: lessons from the 2014 Hazelwood mine fire and 2019-20 Black Summer bushfires.

BACKGROUND: Wildfires cause significant physical and mental ill-health. How physical and mental symptoms interact following wildfire smoke exposure is unclear, particularly in the context of repeated exposures. In this cross-sectional study we investigated how posttraumatic stress and general psychological distress associated with somatic symptoms in a community exposed to multiple smoke events. METHODS: A random weighted sample of 709 adults exposed to smoke during the 2014 Hazelwood coal mine fire in south-eastern Australia completed a survey in 2020. The survey coincided with the Black Summer wildfires that caused a similar period of smoke haze in the region. Participants self-reported somatic symptoms (PHQ-15) and mine fire-related posttraumatic stress (IES-R) experienced over the previous week, general psychological distress (K10) experienced over the previous four weeks, lifetime health diagnoses and demographic information. Associations between posttraumatic stress, general psychological distress, and each PHQ-15 somatic symptom were analysed using ordinal logistic regression models. RESULTS: Overall, 36.2% of participants reported moderate- or high-level somatic symptomology. The most frequent somatic symptoms were fatigue, limb pain, trouble sleeping, back pain, headaches, and shortness of breath. After controlling for confounding factors, general psychological distress and posttraumatic stress were independently associated with all somatic symptoms (except menstrual problems in females for posttraumatic stress). CONCLUSIONS: Results highlight the high prevalence of somatic symptoms and their association with general psychological distress and posttraumatic stress within a community in the midst of a second large-scale smoke event. It is essential that healthcare providers and public health authorities consider the interconnections of these conditions when supporting communities affected by climate-related disasters.

Sociodemographic circumstances, health, and life experience shape posttraumatic distress trajectories among individuals exposed to smoke during a large-scale coal mine fire.

The 2014 Hazelwood coal mine fire in the Latrobe Valley, Australia, distributed toxic smoke into surrounding communities over 45 days. This study investigated risk and protective factors associated with four trajectories of posttraumatic distress (resilient, recovery, delayed-onset, chronic) among exposed adults. Participants (N = 709) completed surveys in 2016-2017 and 2019-2020 assessing mine fire-related particulate matter (PM2.5 ) exposure; sociodemographic, physical, and mental health variables; and exposure to other traumatic and recent stressful events. Mine fire-related posttraumatic distress was measured using the IES-R; trajectories were determined according to established clinical significance thresholds. Relative risk ratios (RRRs) were generated from multivariate multinomial regressions. The resilient trajectory was most common (77.0%). The chronic trajectory (8.5%) was associated with loneliness, RRR = 2.59, 95% CI [1.30, 5.16], and physical health diagnoses, RRR = 2.31, 95% CI [1.32, 4.02]. The delayed-onset trajectory (9.1%) was associated with multiple recent stressful events, RRR = 2.51, 95% CI [1.37, 4.59]; mental health diagnoses, RRR = 2.30, 95% CI [1.25, 4.24]; loneliness, RRR = 2.05, 95% CI [1.09, 3.88]; and male gender, RRR = 2.01, 95% CI [1.18, 3.44]. Socioeconomic advantage protected against chronic, RRR = 0.68, 95% CI [0.53, 0.86], and delayed-onset trajectory membership, RRR = 0.68, 95% CI [0.50, 0.94]; social support protected against chronic trajectory membership, RRR = 0.67, 95% CI [0.49, 0.92]. PM2.5 exposure did not determine trajectory. These findings enhance understanding of longer-term posttraumatic responses to large-scale smoke events and can inform mental health initiatives within at-risk communities.

Divergent receptor utilization is necessary for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections.

Intrapleural injection of cholera toxin B conjugated to saporin (CTB-SAP) mimics respiratory motor neuron death and respiratory deficits observed in rat models of neuromuscular diseases. Seven-day CTB-SAP rats elicit enhanced phrenic long-term facilitation (pLTF) primarily through TrkB and PI3K/Akt-dependent mechanisms [i.e., Gs-pathway, which can be initiated by adenosine 2A (A2A) receptors in naïve rats], whereas 28-day CTB-SAP rats elicit moderate pLTF though BDNF- and MEK-/ERK-dependent mechanisms [i.e., Gq-pathway, which is typically initiated by serotonin (5-HT) receptors in naïve rats]. Here, we tested the hypothesis that pLTF following CTB-SAP is 1) A2A receptor-dependent at 7 days and 2) 5-HT receptor-dependent at 28 days. Adult Sprague-Dawley male rats were anesthetized, paralyzed, ventilated, and exposed to acute intermittent hypoxia (AIH; 3-, 5-min bouts of 10.5% O2) following bilateral, intrapleural injections at 7 days and 28 days of 1) CTB-SAP (25 µg) or 2) unconjugated CTB and SAP (control). Intrathecal C4 delivery included either the 1) A2A receptor antagonist (MSX-3; 10 µM; 12 µL) or 2) 5-HT receptor antagonist (methysergide; 20 mM; 15 µL). pLTF was abolished with A2A receptor inhibition in 7-day, not 28-day, CTB-SAP rats versus controls (P < 0.05), whereas pLTF was abolished following 5-HT receptor inhibition in 28-day, not 7-day, CTB-SAP rats versus controls (P < 0.05). In addition, 5-HT2A receptor expression was unchanged in CTB-SAP rats versus controls, whereas 5-HT2B receptor expression was decreased in CTB-SAP rats versus controls (P < 0.05). This study furthers our understanding of the contribution of differential receptor activation to pLTF and its implications for breathing following respiratory motor neuron death.NEW & NOTEWORTHY The current study investigates underlying receptor-dependent mechanisms contributing to phrenic long-term facilitation (pLTF) following CTB-SAP-induced respiratory motor neuron death at 7 days and 28 days. We found that A2A receptors are required for enhanced pLTF in 7-day CTB-SAP rats, whereas 5-HT receptors are required for moderate pLTF in 28-day CTB-SAP rats. Targeting these time-dependent mechanisms have implications for breathing maintenance over the course of many neuromuscular diseases.

Are e-cigarette use and vaping associated with increased respiratory symptoms and poorer lung function in a population exposed to smoke from a coal mine fire?

BACKGROUND AND OBJECTIVE: E-cigarette use has become increasingly prevalent, but there is some evidence demonstrating potential harms with frequent use. We aimed to identify the profiles of e-cigarette users from a regional community in Australia and investigate the associations of e-cigarettes with respiratory symptoms and lung function. METHODS: A total of 519 participants completed a cross-sectional study. Exposure to e-cigarettes was collected via a validated questionnaire. Respiratory symptoms were evaluated via a self-reported questionnaire and lung function measured with spirometry and forced oscillation technique (FOT). Linear and logistic regression models were fitted to investigate the associations between e-cigarettes and outcomes, while controlling for confounders such as tobacco smoking. RESULTS: Of the 519 participants, 46 (9%) reported e-cigarette use. Users tended to be younger (mean ± SD 45.2 ± 14.5 vs. 55.3 ± 16.0 years in non-users), concurrently using tobacco products (63% vs. 12% in non-users), have a mental health diagnosis (67% vs. 37% in non-users) and have self-reported asthma (63% vs. 42% in non-users). After controlling for known confounders, chest tightness (OR = 2.4, 95% CI 1.2-4.9, p = 0.02) was associated with e-cigarette use. Spirometry was not different after adjustment for confounding. However, FOT showed more negative reactance and a greater area under the reactance curve in e-cigarette users than non-users. CONCLUSION: E-cigarette use was associated with increased asthma symptoms and abnormal lung mechanics in our sample, supporting a potential health risk posed by these products. Vulnerable populations such as young adults and those with mental health conditions have higher usage, while there is high concurrent tobacco smoking.

Amblyomma maculatum-associated rickettsiae in vector tissues and vertebrate hosts during tick feeding.

Rickettsia parkeri, a causative agent of spotted fever rickettsiosis, is transmitted by Amblyomma maculatum (Gulf Coast tick), a tick that may also carry a non-pathogenic spotted fever group Rickettsia, "Candidatus Rickettsia andeanae". Here, we evaluated R. parkeri and "Candidatus R. andeanae" in tissues from A. maculatum prior to, during, and after blood feeding on rabbits. Using colony-reared A. maculatum that were capillary-fed uninfected cells, R. parkeri, "Candidatus R. andeanae", or both rickettsiae, we detected higher levels of Rickettsia spp. in the respective treatment groups. Rickettsial levels increased during blood feeding for both R. parkeri and "Candidatus R. andeanae", with a greater increase in R. parkeri in co-infected ticks compared to singly-infected ticks. We detected transovarial transmission of "Candidatus R. andeanae" in egg and larval cohorts and confirmed vertical transmission of R. parkeri in one group of larvae. Rabbits from all Rickettsia-exposed groups seroconverted on immunofluorescent antibody testing using R. parkeri antigen. Visualization of "Candidatus R. andeanae" in tick salivary glands suggested potential transmission via tick feeding. Here, rickettsial levels in artificially infected ticks demonstrate changes during feeding and transovarial transmission that may be relevant for interpreting rickettsial levels detected in wild A. maculatum.

Associations of atopy and asthma during aging of an adult population over a 20-year follow-up.

OBJECTIVE: Atopy is associated with asthma, but cross-sectional studies suggest this association may be weaker in older adults. It remains unclear if atopy predicts asthma later in adult life. We aimed to investigate whether atopy in young adults predicted asthma 20 years later and to quantify the contemporaneous relationship of atopy and asthma as adults age. METHODS: Participants of the European Community Respiratory Health Survey (ECRHS) in Melbourne aged 20-44 years were followed for 20 years and completed questionnaires, skin prick tests (SPT) and allergen specific immunoglobulin E measurement at a baseline and two subsequent surveys. Using logistic regression and generalized estimating equations, we tested if atopy at baseline predicted current asthma later in life and estimated the association between current atopy measured at each survey and current asthma, while adjusting for potential confounders. RESULTS: The analysis included 220 participants: 50.9% male. Mean (SD) age at baseline was 35.7 (5.7) years. Asthma and atopy prevalence remained stable over 20 years. Baseline atopy (SPT) was associated with current asthma (OR 9.74, 95%CI 4.22, 22.5) over 20 years, and current atopy (SPT) with concurrent asthma (3.12; 1.70, 5.74). CONCLUSIONS: Atopy remains strongly associated with current asthma in 40 to 64 year-old adults, both prospectively and contemporaneously, but the prospective association is stronger.

Use of mobile and cordless phones and change in cognitive function: a prospective cohort analysis of Australian primary school children.

BACKGROUND: Some previous studies have suggested an association between children's use of mobile phones (MPs)/cordless phones (CPs) and development of cognitive function. We evaluated possible longitudinal associations between the use of MPs and CPs in a cohort of primary school children and effects on their cognitive function. METHODS: Data on children's socio-demographics, use of MPs and CPs, and cognitive function were collected at baseline (2010-2012) and follow-up (2012-2013). Cognitive outcomes were evaluated with the CogHealth™ test battery and Stroop Color-Word test. The change in the number of MP/CP voice calls weekly from baseline to follow-up was dichotomized: "an increase in calls" or a "decrease/no change in calls". Multiple linear regression analyses, adjusting for confounders and clustering by school, were performed to evaluate the associations between the change in cognitive outcomes and change in MP and CP exposures. RESULTS: Of 412 children, a larger proportion of them used a CP (76% at baseline and follow-up), compared to a MP (31% at baseline and 43% at follow-up). Of 26 comparisons of changes in cognitive outcomes, four demonstrated significant associations. The increase in MP usage was associated with larger reduction in response time for response inhibition, smaller reduction in the number of total errors for spatial problem solving and larger increase in response time for a Stroop interference task. Except for the smaller reduction in detection task accuracy, the increase in CP usage had no effect on the changes in cognitive outcomes. CONCLUSION: Our study shows that a larger proportion of children used CPs compared to MPs. We found limited evidence that change in the use of MPs or CPs in primary school children was associated with change in cognitive function.

A Prospective Randomized Clinical Trial in Total Hip Arthroplasty-Comparing Early Results Between the Direct Anterior Approach and the Posterior Approach.

BACKGROUND: We report a prospective randomized study comparing early clinical results between the direct anterior approach (DAA) and posterior approach (PA) in primary hip arthroplasty. METHODS: Surgeries were performed by 2 senior hip arthroplasty surgeons. Seventy-two patients with complete data were assessed preoperatively 2, 6, and 12 weeks postoperatively. The primary outcomes were the Western Ontario McMasters Arthritis Index and Oxford Hip Scores. Secondary outcome measures included the EuroQoL, 10-meter walk test, and clinical and radiographic parameters. RESULTS: Data analyses showed no difference between DAA (n = 35) and PA (n = 37) groups when comparing total scores for primary outcomes. No significant differences were observed for 10-meter walk test, EuroQoL, and radiographic analyses. Subgroup analysis for surgeon 1 identified that the DAA group had shorter acute hospital stay, less postoperative opiate requirements, and smaller wounds. However, this was offset by increased operative time, higher intraoperative blood loss, and weaker hip flexion at 2 and 6 weeks. Subgroup analysis of items on the Western Ontario McMasters Arthritis Index and Oxford Hip Score identified that hip flexion activity favored the DAA group up to 6 weeks postoperatively. There was an 83% incidence of lateral cutaneous nerve of thigh neuropraxia at the 12-week mark in the DAA group. No neuropraxias occurred in the PA group. One dislocation occurred in each group. A single patient from the DAA group required reoperation for leg-length discrepancy. CONCLUSION: DAA total hip arthroplasty (THA) has comparable results with PA THA. Choice of surgical approach for THA should be based on patient factors, surgeon preference, and experience.

Use of mobile and cordless phones and cognition in Australian primary school children: a prospective cohort study.

BACKGROUND: Use of mobile (MP) and cordless phones (CP) is common among young children, but whether the resulting radiofrequency exposure affects development of cognitive skills is not known. Small changes have been found in older children. This study focused on children's exposures to MP and CP and cognitive development. The hypothesis was that children who used these phones would display differences in cognitive function compared to those who did not. METHODS: We recruited 619 fourth-grade students (8-11 years) from 37 schools around Melbourne and Wollongong, Australia. Participants completed a short questionnaire, a computerised cognitive test battery, and the Stroop colour-word test. Parents completed exposure questionnaires on their child's behalf. Analysis used multiple linear regression. The principal exposure-metrics were the total number of reported MP and CP calls weekly categorised into no use ('None'); use less than or equal to the median amount ('Some'); and use more than the median ('More'). The median number of calls/week was 2.5 for MP and 2.0 for CP. RESULTS: MP and CP use for calls was low; and only 5 of 78 comparisons of phone use with cognitive measures were statistically significant. The reaction time to the response-inhibition task was slower in those who used an MP 'More' compared to the 'Some' use group and non-users. For CP use, the response time to the Stroop interference task was slower in the 'More' group versus the 'Some' group, and accuracy was worse in visual recognition and episodic memory tasks and the identification task. In an additional exploratory analysis, there was some evidence of a gender effect on mean reaction times. The highest users for both phone types were girls. CONCLUSIONS: Overall, there was little evidence cognitive function was associated with CP and MP use in this age group. Although there was some evidence that effects of MP and CP use on cognition may differ by gender, this needs further exploration. CP results may be more reliable as parents estimated children's phone use and the CPs were at home; results for CP use were broadly consistent with our earlier study of older children.

Assessing Rat Diaphragm Motor Unit Connectivity Outcome Measures as Quantitative Biomarkers of Phrenic Motor Neuron Degeneration and Compensation.

Loss of ventilatory muscle function is a consequence of motor neuron injury and neurodegeneration (e.g., cervical spinal cord injury and amyotrophic lateral sclerosis, respectively). Phrenic motor neurons are the final link between the central nervous system and muscle, and their respective motor units (groups of muscle fibers innervated by a single motor neuron) represent the smallest functional unit of the neuromuscular ventilatory system. Compound muscle action potential (CMAP), single motor unit potential (SMUP), and motor unit number estimation (MUNE) are established electrophysiological approaches that enable the longitudinal assessment of motor unit integrity in animal models over time but have mostly been applied to limb muscles. Therefore, the objectives of this study are to describe an approach in preclinical rodent studies that can be used longitudinally to quantify the phrenic MUNE, motor unit size (represented as SMUP), and CMAP, and then to demonstrate the utility of these approaches in a motor neuron loss model. Sensitive, objective, and translationally relevant biomarkers for neuronal injury, degeneration, and regeneration in motor neuron injury and diseases can significantly aid and accelerate experimental research discoveries to clinical testing.

Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss.

Introduction: Tongue weakness and atrophy can lead to deficits in the vital functions of breathing and swallowing in patients with motor neuron diseases (MNDs; e.g., amyotrophic lateral sclerosis (ALS) and pseudobulbar palsy), often resulting in aspiration pneumonia, respiratory failure, and death. Available treatments for patients with MNDs are largely palliative; thus, there is a critical need for therapies targeting preservation of upper airway function and suggesting a role for tongue exercise in patients with MNDs. Here, we leveraged our inducible rodent model of hypoglossal (XII) motor neuron degeneration to investigate the effects of a strength endurance tongue exercise program on upper airway structure and function. Our model was created through intralingual injection of cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue to induce targeted death of XII motor neurons. Methods: Rats in this study were allocated to 4 experimental groups that received intralingual injection of either CTB-SAP or unconjugated CTB + SAP (i.e., control) +/- tongue exercise. Following tongue exercise exposure, we evaluated the effect on respiratory function (via plethysmography), macrostructure [via magnetic resonance imaging (MRI) of the upper airway and tongue], and ultrafine structure [via ex vivo magnetic resonance spectroscopy (MRS) of the tongue] with a focus on lipid profiles. Results: Results showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to CTB-SAP + exercise rats and control rats +/- tongue exercise, which was ameliorated with tongue exercise. Additionally, CTB-SAP + sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP + exercise rats or control rats +/- tongue exercise. Conclusion: These findings provide further evidence that a strength endurance tongue exercise program may be a viable therapeutic treatment option in patients with XII motor neuron degeneration in MNDs such as ALS. Future directions will focus on investigating the underlying mechanism responsible for tongue exercise-induced plasticity in the hypoglossal-tongue axis, particularly inflammatory associated factors such as BDNF.

What impact did the COVID-19 pandemic have on psychosis and the delivery of early intervention psychosis services?

BACKGROUND: In Australia, the first nationwide COVID-19 lockdown occurred in March 2020 bringing challenges for early intervention psychosis (EIP) services. Limited evidence exists on the impacts of the pandemic on treatment outcomes among EIP clients. METHODS: This prospective cohort study analysed routine data from 15 headspace Early Psychosis centres in Australia. Participants were 12 to 25 years, meeting criteria for First Episode Psychosis (FEP) or Ultra High Risk of psychosis (UHR) comparing those who commenced treatment 'pre-COVID-19' (between 16th August 2018 and 15th August 2019), and 'during-COVID-19' (between 1st March 2020 and 15th September 2020). Clinical symptoms at treatment commencement were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Kessler Psychological Distress Scale (K10). with outcomes after 6 months compared between cohorts using linear mixed-effects regression, controlling for confounders. RESULTS: Of 1246 young people analysed (653 FEP, 596 UHR), significant improvements were observed with treatment in both groups (5 to 13-point reduction in BPRS score per 6-months treatment). Treatment effectiveness reduced during-COVID-19 for psychosis symptoms, with the FEP BPRS treatment effect lower by 4.3 points (95%CI: 0.5, 8.1). UHR clients had lower BPRS negative symptoms during-COVID-19 (p = 0.020). Service contacts increased during-COVID-19, with increased telehealth services (p < 0.001). CONCLUSIONS: Early intervention remained effective for FEP and UHR, despite the pandemic and transition of EIP services to virtual service delivery. Reduced treatment efficacy in FEP psychosis symptoms may indicate potential limitations of telehealth. Further research to examine longer term clinical and functional outcomes due to the pandemic is required.