Replicability, adaptability and long-term impact of the 'Healthy Youngsters, Healthy Dads' program in Newcastle, Australia.

'Healthy Youngsters, Healthy Dads' (HYHD) targets fathers to improve the health of their preschool-aged children. In a previous randomized trial, fathers and children experienced meaningful improvements in physical activity and eating behaviours. The next phase is to test the replicability and adaptability of HYHD when delivered in the community by trained facilitators. Fathers/father-figures and children aged 3-5 years were recruited from Newcastle, Australia into a 9-week, non-randomized trial with assessments at baseline, 10 weeks, and 12 months. The primary outcome was achievement of pre-registered targets for recruitment (≥ 96 dyads), attendance (≥ 70%), compliance (completing ≥ 70% of home-based tasks), fidelity (≥ 80% of content delivered as intended) and program satisfaction (≥ 4/5). Secondary outcomes included physical activity, nutrition, screen time and parenting measures. Process targets were surpassed for recruitment (140 fathers, 141 children), attendance (79% for fathers-only workshops, 81% for father-child sessions), compliance (80% of home-tasks completed), fidelity (99% for education, ≥ 97% for practical) and program satisfaction (4.8/5). Mixed effects regression models revealed significant effects in fathers for moderate-to-vigorous physical activity, co-physical activity, dietary intake and parenting practises, which were maintained at 12 months. Significant effects were also established for screen time at 10 weeks only. For children, significant effects were observed for screen time and dietary intake at 10 weeks, while effects on energy-dense, nutrient-poor foods and healthy, nutrient-dense core food intake were maintained at 12 months. Findings demonstrate the replicability and adaptability of HYHD when delivered in the community by local trained facilitators. Further investigation into how to optimally scale-up HYHD is warranted.

International trends in prescribing extended wear soft contact lenses (2000-2023): An update.

PURPOSE: Extended wear has long been considered as the ultimate contact lens modality in terms of user convenience. The purpose of this work is to update earlier surveys by describing international trends in extended wear soft lens fitting between 2000 and 2023, inclusive. METHOD: An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023, inclusive. Data relating to 282,142 soft contact lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of extended wear soft lens fitting. RESULTS: Over the duration of the work there was a very small decrease in the prescribing of extended wear soft lenses (p < 0.0001). More detailed inspection shows that prescribing of these lenses steadily increased from 5.8 % of all soft lens fits in 2000 to 11.6 % in 2007, then steadily decreased to 5.2 % in 2023. Of all soft contact lenses prescribed to males, 9.2 % were fitted for extended wear, compared with 6.7 % for females (p < 0.0001). The mean age of extended wear soft lens wearers at fitting was 34.7 ± 14.7 years, compared to 31.1. ± 14.10 years for daily soft lens wearers (p < 0.0001). Analysis of 1,948 recent extended wear soft lens fits (2019-2023, inclusive), in terms of material type, revealed that, on average, 86 % and 14 % of extended wear soft lenses were fitted using silicone hydrogel and hydrogel materials, respectively. CONCLUSION: A modest increase in extended wear soft lens prescribing from 2000 to 2007 corresponded with the introduction of high oxygen transmissibility silicone hydrogel lenses. However, prescribing of this lens type declined thereafter, probably due to ongoing concerns over their increased rate of microbial keratitis, resulting in a prescribing rate in 2023 (5.2%) that was little different to that observed in 2000 (5.8%).

International trends in prescribing toric soft contact lenses to correct astigmatism (2000-2023): An update.

PURPOSE: There have been significant advancements in toric soft contact lens design and manufacturing technology, and increased product availability, over the past half a century. The purpose of this work is to update earlier surveys by describing international trends in toric soft lens fitting between 2000 and 2023, inclusive. METHOD: An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023, inclusive. Data relating to 220,934 standard soft daily wear single vision lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of toric soft lens fitting. RESULTS: Overall, toric soft lens prescribing almost doubled over the time-course of this survey, from 24.4 % of standard soft daily wear single vision lens fits in 2000 to 46.2 % in 2023 (p < 0.0001). There were significant differences between countries in toric soft lens prescribing (p < 0.0001). Of all standard soft daily wear single vision contact lenses prescribed to males, 32.0 % were toric soft lenses, compared with 28.7 % for females (p < 0.0001). The mean age of toric soft lens wearers was 30.5 ± 12.5 years, compared to 27.9. ± 12.1 years for spherical soft lens wearers (p < 0.0001). Analysis of 13,582 recent toric soft lens fits (2019-2023, inclusive), in terms of material type and replacement frequency, revealed the following proportions: reusable silicone hydrogel - 51 %; daily disposable silicone hydrogel - 27 %; daily disposable hydrogel - 12 %; and reusable hydrogel - 10 %. CONCLUSION: There has been a substantial increase in toric soft lens fitting throughout the 24 years of this survey, to a point whereby almost all clinically significant astigmatism is being corrected among those wearing standard soft daily wear single vision lenses.

Current teachers' perceptions and students' perspectives regarding activities modalities, instructional settings during primary school physical education classes in China: a cross-sectional observational study.

Introduction: This study set out to understand the association between teaching practices, teacher confidence, competence, self-efficacy, and the resulting student outcomes. Methods: Data regarding teaching behaviours were collected via video recording and then evaluated using the MASTER Observation Tool. The information about demographics, self-reported teaching confidence, competence, self-efficacy, and student outcomes was collected using questionnaires. The association between teacher characteristics, and teacher and/or student outcome variables were tested using a one-way analysis of variance (ANOVA). Results: A total of ten primary schools were involved, including 597 children (age range: 10-12 years, grade 4-6) and 16 grade 4-6 PE teachers (with 16 PE classes). Most of the Physical Education (PE) lesson time was spent in training-form activities (60.2% ± 9.1), followed by instructional time (33.1% ± 8.6%), reflection (3.4% ± 2.3%), and warm-up (2.9% ± 2.0 %). It was observed that teaching behaviours and student outcomes were significantly better in urban than rural areas. Smaller class sizes (21-30 children) were found to have more positive feedback than larger ones (41-50 children). PE teachers with more than 10 years of teaching experience reported more teaching competence and self-efficacy than teachers with less than 10 years of experience. PE teachers with class sizes of 21-30 children enjoyed significantly better scores in self-efficacy than classes with 41-50 children. They also scored more highly in confidence and competence than classes with 41-50 and 51-60 pupils. Conclusion: The current study confirmed that teachers dedicated a large proportion of lesson time to PE delivering training-form activities, followed by instructional time. Teaching behaviour and student outcomes were associated with location and class size, but not gender. The study contributes to our understanding of PE instruction in Chinese primary schools and offers preliminary evidence to improve future PE teaching strategies in the country.

International trends in daily disposable contact lens prescribing (2000-2023): An update.

PURPOSE: Daily disposable contact lenses offer numerous benefits in terms of ocular health and wearer convenience. The purpose of this work is to update earlier surveys by describing global trends in daily disposable lens fitting between 2000 and 2023. METHOD: An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023, inclusive. Data relating to 265,106 daily wear soft lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of daily disposable lens fitting. RESULTS: Overall, daily disposable lens prescribing increased over time, from 17.1 % of daily wear soft lens fits in 2000 to 46.7 % in 2023 (p < 0.0001). There were significant differences between countries in daily disposable lens prescribing (p < 0.0001), and between the percentage of males fitted with daily disposable lenses, as a proportion of all daily wear soft lenses (37.2 %), compared to females (35.2 %) (p < 0.0001). Daily disposable lens wearers are slightly younger at fitting than reusable soft lens wearers (31.0 vs 31.2 years, respectively) (p < 0.0001), although this difference is not clinically meaningful. Analysis of 50,240 daily wear soft lenses fitted recently (2019-2023) were found to be prescribed for the following replacement frequencies: daily - 47 %; monthly - 42 %; 1-2 weekly - 9 %; and ≥3 monthly - 2 %. CONCLUSION: There has been a substantial increase in daily disposable lens fitting throughout the first 24 years of this century. The gradual nature of this increase is commensurate with the staged introduction of daily disposable lens designs and expanded parameter ranges over the survey period.

International trends in rigid contact lens prescribing (2000-2023): An update.

PURPOSE: Rigid contact lenses have an important role in contact lens practice. The purpose of this work is to update earlier surveys by describing global trends in rigid lens fitting between 2000-2023. METHOD: An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023. Data relating to 342,500 fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of rigid lens fitting, defined as the fitting of any design of a contact lens manufactured in a rigid material. RESULTS: Overall, rigid lens prescribing increased slightly over time, from 14.2 % of lens fits in 2000 to 15.2 % in 2023 (p < 0.0001). However, post-hoc analysis shows that the change over time is best described as a decline between 2000 and 2012, followed by a steady increase subsequently. There were significant differences in rigid lens prescribing between countries (p < 0.0001). The difference between the percentage of males fitted with rigid lenses, as a proportion of all contact lenses (12.7 %), and females (12.0 %) is significant (p < 0.0001), although not clinically meaningful. Rigid lens wearers are older at fitting than soft lens wearers (38.7 vs 31.3 years, respectively) (p < 0.0001). Analysis of 5,994 rigid lens fits prescribed currently (2019-2023) were categorised as: corneal sphere - 30 %; scleral and corneo-scleral - 28 %; corneal myopia control/orthokeratology - 21 %; and corneal complex (including toric, multifocal and monovision) - 16 %. CONCLUSION: There has been a slight increase in rigid lens fitting during the second decade of this century. This increase is apparently due to a 'repurposing' of rigid lenses, with the growth of scleral/corneo-scleral and myopia control/orthokeratology lens fits essentially replacing conventional spherical corneal lens fits.

Temporal variations in meibomian gland structure-A pilot study.

PURPOSE: To investigate whether there is a measurable change in meibomian gland morphological characteristics over the course of a day (12 h) and over a month. METHODS: The study enrolled 15 participants who attended a total of 11 study visits spanning a 5-week period. To assess diurnal changes in meibomian glands, seven visits were conducted on a single day, each 2 h apart. For monthly assessment, participants attended an additional visit at the same time of the day every week for three consecutive weeks. Meibography using the LipiView® II system was performed at each visit, and meibomian gland morphological parameters were calculated using custom semi-automated software. Specifically, six central glands were analysed for gland length ratio, gland width, gland area, gland intensity and gland tortuosity. RESULTS: The average meibomian gland morphological metrics did not exhibit significant changes during the course of a day or over a month. Nonetheless, certain individual gland metrics demonstrated notable variation over time, both diurnally and monthly. Specifically, meibomian gland length ratio, area, width and tortuosity exhibited significant changes both diurnally and monthly when assessed on a gland-by-gland basis. CONCLUSIONS: Meibomian glands demonstrated measurable structural change over short periods of time (hours and days). These results have implications for innovation in gland imaging and for developing precision monitoring of gland structure to assess meibomian gland health more accurately.

BCLA CLEAR Presbyopia: Definitions.

Presbyopia is often the first sign of ageing experienced by humans. Standardising terminology and adopting it across the BCLA CLEAR Presbyopia reports, improves consistency in the communication of the evidence-based understanding of this universal physiological process. Presbyopia can be functionally and psychologically debilitating, especially for those with poor access to eyecare. Presbyopia was defined as occurring when the physiologically normal age-related reduction in the eye's focusing range reaches a point that, when optimally corrected for far vision, the clarity of vision at near is insufficient to satisfy an individual's requirements. Accommodation is the change in optical power of the eye due to a change in crystalline lens shape and position, whereas pseudo-accommodation is the attainment of functional near vision in an emmetropic or far-corrected eye without changing the refractive power of the eye. Other definitions specific to vision and lenses for presbyopia were also defined. It is recommended that these definitions be consistently adopted in order to standardise future research, clinical evaluations and education.

BCLA CLEAR Presbyopia: Management with contact lenses and spectacles.

This paper seeks to outline the history, market situation, clinical management and product performance related to the correction of presbyopia with both contact lenses and spectacles. The history of the development of various optical forms of presbyopic correction are reviewed, and an overview is presented of the current market status of contact lenses and spectacles. Clinical considerations in the fitting and aftercare of presbyopic contact lens and spectacle lens wearers are presented, with general recommendations for best practice. Current options for contact lens correction of presbyopia include soft simultaneous, rigid translating and rigid simultaneous designs, in addition to monovision. Spectacle options include single vision lenses, bifocal lenses and a range of progressive addition lenses. The comparative performance of both contact lens and spectacle lens options is presented. With a significant proportion of the global population now being presbyopic, this overview is particularly timely and is designed to act as a guide for researchers, industry and eyecare practitioners alike.

BCLA CLEAR Presbyopia: Evaluation and diagnosis.

It is important to be able to measure the range of clear focus in clinical practice to advise on presbyopia correction techniques and to optimise the correction power. Both subjective and objective techniques are necessary: subjective techniques (such as patient reported outcome questionnaires and defocus curves) assess the impact of presbyopia on a patient and how the combination of residual objective accommodation and their natural DoF work for them; objective techniques (such as autorefraction, corneal topography and lens imaging) allow the clinician to understand how well a technique is working optically and whether it is the right choice or how adjustments can be made to optimise performance. Techniques to assess visual performance and adverse effects must be carefully conducted to gain a reliable end-point, considering the target size, contrast and illumination. Objective techniques are generally more reliable, can help to explain unexpected subjective results and imaging can be a powerful communication tool with patients. A clear diagnosis, excluding factors such as binocular vision issues or digital eye strain that can also cause similar symptoms, is critical for the patient to understand and adapt to presbyopia. Some corrective options are more permanent, such as implanted inlays / intraocular lenses or laser refractive surgery, so the optics can be trialled with contact lenses in advance (including differences between the eyes) to better communicate with the patient how the optics will work for them so they can make an informed choice.

Gaze and behavioural metrics in the refractive correction of presbyopia.

PURPOSE: To investigate gaze and behavioural metrics at different viewing distances with multifocal contact lenses (MFCLs), single vision contact lenses (SVCLs) and progressive addition lenses (PALs). METHODS: Fifteen presbyopic contact lens wearers participated over five separate study visits. At each visit, participants were randomly assigned to wear one of five refractive corrections: habitual PAL spectacles, delefilcon A (Alcon Inc.) MFCLs and three separate pairs of delefilcon A single vision lenses worn as distance, intermediate and near corrections. Participants wore a Pupil Core headset to record eye and head movements while performing three visual tasks: reading, visual search and scene observation. Data were investigated using linear regression and post-hoc testing. Parameters of interest included gaze (fixation duration, head movement) and behavioural (reading speed, reading accuracy, visual search time) metrics. RESULTS: Reading speed in SVCLs was significantly faster than in MFCLs and PAL spectacles (F = 16.3, p < 0.0001). Refractive correction worn did not influence visual search times (F = 0.16, p = 0.85). Fixation duration was significantly affected by the type of visual task (F = 60.2, p < 0.001), and an interaction effect was observed between viewing distance and refractive correction (F = 4.3, p = 0.002). There was significantly more horizontal and vertical head movement (F = 3.2, p = 0.01 and F = 3.3, p = 0.01, respectively) during visual search tasks when wearing PAL spectacles compared to SVCLs or MFCLs. CONCLUSION: This work showed that the type of refractive correction affects behavioural metrics such as reading speed and gaze behaviour by affecting horizontal and vertical head movements. The findings of this study suggest that under certain conditions, wearers of MFCLs make fewer head movements compared to PAL spectacles. Gaze behaviour metrics offer a new approach to compare and understand contact lens and spectacle performance, with potential applications including peripheral optical designs for myopia management.

Interferon-gamma contributes to disease progression in the Ndufs4(-/-) model of Leigh syndrome.

AIM: Leigh syndrome (LS), the most common paediatric presentation of genetic mitochondrial dysfunction, is a multi-system disorder characterised by severe neurologic and metabolic abnormalities. Symmetric, bilateral, progressive necrotizing lesions in the brainstem are defining features of the disease. Patients are often symptom free in early life but typically develop symptoms by about 2 years of age. The mechanisms underlying disease onset and progression in LS remain obscure. Recent studies have shown that the immune system causally drives disease in the Ndufs4(-/-) mouse model of LS: treatment of Ndufs4(-/-) mice with the macrophage-depleting Csf1r inhibitor pexidartinib prevents disease. While the precise mechanisms leading to immune activation and immune factors involved in disease progression have not yet been determined, interferon-gamma (IFNγ) and interferon gamma-induced protein 10 (IP10) were found to be significantly elevated in Ndufs4(-/-) brainstem, implicating these factors in disease. Here, we aimed to explore the role of IFNγ and IP10 in LS. METHODS: To establish the role of IFNγ and IP10 in LS, we generated IFNγ and IP10 deficient Ndufs4(-/-)/Ifng(-/-) and Ndufs4(-/-)/IP10(-/-) double knockout animals, as well as IFNγ and IP10 heterozygous, Ndufs4(-/-)/Ifng(+/-) and Ndufs4(-/-)/IP10(+/-), animals. We monitored disease onset and progression to define the impact of heterozygous or homozygous loss of IFNγ and IP10 in LS. RESULTS: Loss of IP10 does not significantly impact the onset or progression of disease in the Ndufs4(-/-) model. IFNγ loss significantly extends survival and delays disease progression in a gene dosage-dependent manner, though the benefits are modest compared to Csf1r inhibition. CONCLUSIONS: IFNγ contributes to disease onset and progression in LS. Our findings suggest that IFNγ targeting therapies may provide some benefits in genetic mitochondrial disease, but targeting IFNγ alone would likely yield only modest benefits in LS.

End-of-day assessment of asymptomatic versus highly symptomatic soft contact lens wearers.

PURPOSE: To investigate differences in key clinical parameters between asymptomatic and highly symptomatic soft contact lens (CL) wearers after 14 h of wear. METHODS: In this pilot investigation, Phase 1 identified asymptomatic (CLDEQ-8 score ≤ 7) and highly symptomatic (CLDEQ-8 score ≥ 20) subjects after fitting with nelfilcon A CLs. Phase 2 investigated the following over a single nelfilcon A CL-wearing day (14 ± 2 h): blinking characteristics, tear meniscus height (TMH), non-invasive tear break-up time (NIBUT), tear film osmolarity and eyelid margin staining. Parameters for the two groups were compared using linear mixed models and post-hoc testing. The relationship between comfort scores and the clinical parameters was also investigated. RESULTS: Overall, 161 and 42 subjects were enrolled into Phase 1 and 2, respectively. Twenty-five asymptomatic and 17 symptomatic subjects completed Phase 2. Lower eyelid TMH was decreased after 14 h in symptomatic compared with asymptomatic subjects (least square mean [LSM] difference -0.04 mm, 95% CI: -0.07, -0.01). Osmolarity was lower in symptomatic than in asymptomatic subjects at fitting (LSM difference -9.89, 95% CI: -18.91, -0.86). Upper eyelid margin staining was greater after 14 h in symptomatic than in asymptomatic subjects (LSM difference 0.53, 95% CI: 0.01, 1.05) and greater after 14 h than baseline in the symptomatic group (LSM difference 0.61, 95% CI: 0.16, 1.07). There was a significant relationship between comfort and upper eyelid margin staining (r = -0.40, 95% CI: -0.63, -0.11) and blink rate (r = -0.31, 95% CI: -0.57, -0.003). CONCLUSION: The potential parameters most effective in differentiating asymptomatic from symptomatic wearers were upper eyelid margin staining and lower TMH. The parameter with the strongest relationship to comfort was upper eyelid margin staining, where higher comfort scores were associated with lower levels of staining.

Pilot randomized controlled trial of a game-based intervention for teaching basketball in Chinese primary school physical education.

This study aimed to examine the preliminary efficacy and feasibility of implementing a tailored version of the MASTER coach education programme in Chinese primary schools to support physical education (PE) teachers' basketball lesson design and delivery. A total of 20 primary schools in Beijing, China were recruited, with one PE teacher and their class (N = 715 students aged 10-13 yrs) from each school included in the study and randomly allocated to the MASTER intervention (n = 10) or control group (n = 10). Compared to the control group, a significant difference was observed in the MASTER group for the proportion of playing-form activities delivered during PE (27.65, 95% CI [20.27, 35.03]) and for teachers' perceptions of confidence (23.92, 95% CI [15.87, 31.92]) and competence (24.12, 95% CI [10.28, 24.71]) to teach. Significant differences between groups were observed for students' perceived athletic competence (3.56%; 95% CI [3.15, 3.96]), enjoyment (11.83%; 95% CI [10.98, 12.69]), well-being (8.51%; 95% CI [7.02, 10.00]), intrinsic motivation (+0.74%; 95% CI [0.30, 1.17]), introjected motivation (-2.24%; 95% CI [-2.77, -1.70]), and external motivation (-0.49%; 95% CI [-0.90, -0.08]). The MASTER programme was effective in improving teaching practices in Chinese primary schools, and in facilitating improvements in teacher and student outcomes.

Impact of dietary ketosis on volatile anesthesia toxicity in a model of Leigh syndrome.

BACKGROUND: Genetic mitochondrial diseases impact over 1 in 4000 individuals, most often presenting in infancy or early childhood. Seizures are major clinical sequelae in some mitochondrial diseases including Leigh syndrome, the most common pediatric presentation of mitochondrial disease. Dietary ketosis has been used to manage seizures in mitochondrial disease patients. Mitochondrial disease patients often require surgical interventions, leading to anesthetic exposures. Anesthetics have been shown to be toxic in the setting of mitochondrial disease, but the impact of a ketogenic diet on anesthetic toxicities in this setting has not been studied. AIMS: Our aim in this study was to determine whether dietary ketosis impacts volatile anesthetic toxicities in the setting of genetic mitochondrial disease. METHODS: The impact of dietary ketosis on toxicities of volatile anesthetic exposure in mitochondrial disease was studied by exposing young Ndufs4(-/-) mice fed ketogenic or control diet to isoflurane anesthesia. Blood metabolites were measured before and at the end of exposures, and survival and weight were monitored. RESULTS: Compared to a regular diet, the ketogenic diet exacerbated hyperlactatemia resulting from isoflurane exposure (control vs. ketogenic diet in anesthesia mean difference 1.96 mM, Tukey's multiple comparison adjusted p = .0271) and was associated with a significant increase in mortality during and immediately after exposures (27% vs. 87.5% mortality in the control and ketogenic diet groups, respectively, during the exposure period, Fisher's exact test p = .0121). Our data indicate that dietary ketosis and volatile anesthesia interact negatively in the setting of mitochondrial disease. CONCLUSIONS: Our findings suggest that extra caution should be taken in the anesthetic management of mitochondrial disease patients in dietary ketosis.

The participation of Aboriginal and Torres Strait Islander parents in Australian trials of parenting programs for improving children's health: a scoping review.

OBJECTIVES: To assess the inclusion of Aboriginal and Torres Strait Islander parents in trials of parenting programs in Australia; the involvement of Indigenous fathers in such studies; and whether parenting programs are designed to be culturally appropriate for Aboriginal and Torres Strait Islander people. STUDY DESIGN: Scoping review of peer-reviewed journal publications that report quantitative outcomes for Australian randomised control trials of parenting programs in which the participants were parents or caregivers of children under 18 years of age, and with at least one outcome related to children's health, health behaviour, or wellbeing. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus databases. DATA SYNTHESIS: Of 109 eligible publications, nine reported how many participants were Aboriginal or Torres Strait Islander people; three specified whether they were Aboriginal, Torres Strait Islander, or both. Two publications described specific interventions for Aboriginal and Torres Strait Islander children; both reported consultation with Indigenous people regarding program design. Of the 15 559 participating parents in all included publications, 93 were identified as Aboriginal or Torres Strait Islander people. No publications noted as study limitations the absence of consultation with Indigenous people or the low participation rate of Aboriginal and Torres Strait Islander families. CONCLUSIONS: The specific needs and interests of Aboriginal and Torres Strait Islander families have not generally been considered in Australian trials of parenting programs that aim to improve the mental and physical health of children. Further, Indigenous people are rarely involved in the planning and implementation of the interventions, few of which are designed to be culturally appropriate for Indigenous people. If parenting research in Australia is to support Aboriginal and Torres Strait Islander families, it must include consultation with local communities, adapt interventions and research methods to the needs of the participating parents and their communities, and improve the recruitment and retention of Aboriginal and Torres Strait Islander participants.

Potassium Leak Channels and Mitochondrial Complex I Interact in Glutamatergic Interneurons of the Mouse Spinal Cord.

BACKGROUND: Volatile anesthetics induce hyperpolarizing potassium currents in spinal cord neurons that may contribute to their mechanism of action. They are induced at lower concentrations of isoflurane in noncholinergic neurons from mice carrying a loss-of-function mutation of the Ndufs4 gene, required for mitochondrial complex I function. The yeast NADH dehydrogenase enzyme, NDi1, can restore mitochondrial function in the absence of normal complex I activity, and gain-of-function Ndi1 transgenic mice are resistant to volatile anesthetics. The authors tested whether NDi1 would reduce the hyperpolarization caused by isoflurane in neurons from Ndufs4 and wild-type mice. Since volatile anesthetic behavioral hypersensitivity in Ndufs4 is transduced uniquely by glutamatergic neurons, it was also tested whether these currents were also unique to glutamatergic neurons in the Ndufs4 spinal cord. METHODS: Spinal cord neurons from wild-type, NDi1, and Ndufs4 mice were patch clamped to characterize isoflurane sensitive currents. Neuron types were marked using fluorescent markers for cholinergic, glutamatergic, and γ-aminobutyric acid-mediated (GABAergic) neurons. Norfluoxetine was used to identify potassium channel type. Neuron type-specific Ndufs4 knockout animals were generated using type-specific Cre-recombinase with floxed Ndufs4. RESULTS: Resting membrane potentials (RMPs) of neurons from NDi1;Ndufs4, unlike those from Ndufs4, were not hyperpolarized by 0.6% isoflurane (Ndufs4, ΔRMP -8.2 mV [-10 to -6.6]; P = 1.3e-07; Ndi1;Ndufs4, ΔRMP -2.1 mV [-7.6 to +1.4]; P = 1). Neurons from NDi1 animals in a wild-type background were not hyperpolarized by 1.8% isoflurane (wild-type, ΔRMP, -5.2 mV [-7.3 to -3.2]; P = 0.00057; Ndi1, ΔRMP, 0.6 mV [-1.7 to 3.2]; P = 0.68). In spinal cord slices from global Ndufs4 animals, holding currents (HC) were induced by 0.6% isoflurane in both GABAergic (ΔHC, 81.3 pA [61.7 to 101.4]; P = 2.6e-05) and glutamatergic (ΔHC, 101.2 pA [63.0 to 146.2]; P = 0.0076) neurons. In neuron type-specific Ndufs4 knockouts, HCs were increased in cholinergic (ΔHC, 119.5 pA [82.3 to 156.7]; P = 0.00019) and trended toward increase in glutamatergic (ΔHC, 85.5 pA [49 to 126.9]; P = 0.064) neurons but not in GABAergic neurons. CONCLUSIONS: Bypassing complex I by overexpression of NDi1 eliminates increases in potassium currents induced by isoflurane in the spinal cord. The isoflurane-induced potassium currents in glutamatergic neurons represent a potential downstream mechanism of complex I inhibition in determining minimum alveolar concentration.