Energy cost and return for hunting in African wild dogs and Cheetahs

African wild dogs (Lycaon pictus) are reported to hunt with energetically costly long chase distances. We used high-resolution GPS and inertial technology to record 1,119 high-speed chases of all members of a pack of six adult African wild dogs in northern Botswana. Dogs performed multiple short, high-speed, mostly unsuccessful chases to capture prey, while cheetahs (Acinonyx jubatus) undertook even shorter, higher-speed hunts. We used an energy balance model to show that the energy return from group hunting and feeding substantially outweighs the cost of multiple short chases, which indicates that African wild dogs are more energetically robust than previously believed. Comparison with cheetah illustrates the trade-off between sheer athleticism and high individual kill rate characteristic of cheetahs, and the energetic robustness of frequent opportunistic group hunting and feeding by African wild dogs

Auditory and vestibular function in mitochondrial patients harbouring the m.3243A>G variant

\ua9 2024 The Author(s).Hearing impairment is a frequent clinical feature in patients with mitochondrial disease harbouring the pathogenic variant, m.3243A>G. However, auditory neural dysfunction, its perceptual consequences and implications for patient management are not established. Similarly, the association with vestibular impairment has not yet been explored. This case-control study investigated in 12 adults with genetically confirmed m.3243A>G adults [9 females; 45.5 \ub1 16.3 years (range 18-66); 47.1 \ub1 21.5 hearing level, dB] compared with 12 age, sex and hearing level-matched controls with sensory (cochlear level) hearing loss [9 females; 46.6 \ub1 11.8 years (range 23-59); 47.7 \ub1 25.4 hearing level, dB]. Participants underwent a battery of electroacoustic, electrophysiologic and perceptual tests, which included pure tone audiometry, otoacoustic emissions, auditory brainstem responses, auditory temporal processing measures, monaural/binaural speech perception, balance and vestibular testing and self-reported questionnaires (dizziness and hearing disability). Our findings showed evidence of auditory neural abnormality and perceptual deficits greater than expected for cochlear pathology. Compared with matched controls with sensory hearing loss, adults with mitochondrial disease harbouring m.3243A>G had abnormal electrophysiologic responses from the VIII nerve and auditory brainstem (P = 0.005), an impaired capacity to encode rapidly occurring acoustic signal changes (P = 0.005), a reduced ability to localize sound sources (P = 0.028) and impaired speech perception in background noise (P = 0.008). Additionally, vestibular dysfunction (P = 0.011), greater perceived dizziness (P = 0.001) and reduced stance time (balance, P = 0.009) were also seen in participants with m.3243A>G mitochondrial disease when compared with matched counterparts. This pilot study revealed that auditory evaluation including evoked potential responses from the auditory nerve/brainstem and speech perception in noise tests should form an important part of the management for individuals with m.3243A>G-related mitochondrial disease. Those presenting with hearing impairment and symptoms concerning balance and dizziness should undergo vestibular testing and appropriate management

Qualitative study of fatigue in adults with primary mitochondrial disease: Development of the PROMIS Fatigue Mitochondrial Disease Short Form

\ua9 2025Background: Fatigue is a debilitating symptom in patients with primary mitochondrial disease nPMD). Developing new treatments that improve fatigue is a patient priority but is hampered by a lack of fit-for-purpose patient-reported outcome measures (PROMs). We aimed to understand the impact of fatigue on the lives of people with PMD and develop a brief PMD-specific PROM to evaluate fatigue in clinical trials. Methods: Adults with genetically confirmed PMD and self-reported moderate-to-severe fatigue and myopathy/exercise intolerance participated in a concept elicitation interview to explore their experiences of fatigue. Interview transcripts were coded thematically using MAXQDA™. Characteristics and impacts that emerged from the interviews were mapped to items in the PROMIS\uae Fatigue item bank. Participants then engaged in a cognitive interview to assess relevance and understandability of PROMIS Fatigue items considered for the PROM. Results: Twelve adults with PMD (n = 8 women, age 20–75 years) were interviewed. The most frequently reported characteristics of fatigue included tiredness, muscle weakness/fatigue, exhaustion, lack of energy, and mental fatigue. Fatigue affected patients\u27 ability to perform daily life activities, including household chores, leisure activities, physical activity/exercise, and work/school, and negatively affected mood and relationships. Nine items were included in the final PROM based on level of endorsement of underlying concepts elicited by the concept elicitation interviews and relevance, clarity, and ease of answering, as assessed in the cognitive interviews. Conclusion: The nine-item PROMIS Fatigue Mitochondrial Disease Short Form is the first PROM designed specifically to assess fatigue in PMD. This study demonstrates the content validity of the short form, and future longitudinal studies will assess its psychometric properties

Common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project

Objectives The common data elements (CDE) project was developed by the National Institute of Neurological Disorders and Stroke (NINDS) to provide clinical researchers with tools to improve data quality and allow for harmonization of data collected in different research studies. CDEs have been created for several neurological diseases; the aim of this project was to develop CDEs specifically curated for mitochondrial disease (Mito) to enhance clinical research. Methods Nine working groups (WGs), composed of international mitochondrial disease experts, provided recommendations for Mito clinical research. They initially reviewed existing NINDS CDEs and instruments, and developed new data elements or instruments when needed. Recommendations were organized, internally reviewed by the Mito WGs, and posted online for external public comment for a period of eight weeks. The final version was again reviewed by all WGs and the NINDS CDE team prior to posting for public use

Can improving working memory prevent academic difficulties? A school based randomised controlled trial.

BACKGROUND: Low academic achievement is common and is associated with adverse outcomes such as grade repetition, behavioural disorders and unemployment. The ability to accurately identify these children and intervene before they experience academic failure would be a major advance over the current 'wait to fail' model. Recent research suggests that a possible modifiable factor for low academic achievement is working memory, the ability to temporarily store and manipulate information in a 'mental workspace'. Children with working memory difficulties are at high risk of academic failure. It has recently been demonstrated that working memory can be improved with adaptive training tasks that encourage improvements in working memory capacity. Our trial will determine whether the intervention is efficacious as a selective prevention strategy for young children at risk of academic difficulties and is cost-effective. METHODS/DESIGN: This randomised controlled trial aims to recruit 440 children with low working memory after a school-based screening of 2880 children in Grade one. We will approach caregivers of all children from 48 participating primary schools in metropolitan Melbourne for consent. Children with low working memory will be randomised to usual care or the intervention. The intervention will consist of 25 computerised working memory training sessions, which take approximately 35 minutes each to complete. Follow-up of children will be conducted at 6, 12 and 24 months post-randomisation through child face-to-face assessment, parent and teacher surveys and data from government authorities. The primary outcome is academic achievement at 12 and 24 months, and other outcomes include child behaviour, attention, health-related quality of life, working memory, and health and educational service utilisation. DISCUSSION: A successful start to formal learning in school sets the stage for future academic, psychological and economic well-being. If this preventive intervention can be shown to be efficacious, then we will have the potential to prevent academic underachievement in large numbers of at-risk children, to offer a ready-to-use intervention to the Australian school system and to build international research partnerships along the health-education interface, in order to carry our further studies of effectiveness and generalisability.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Therapeutic effects of the mitochondrial ROS-redox modulator KH176 in a mammalian model of Leigh Disease

Leigh Disease is a progressive neurometabolic disorder for which a clinical effective treatment is currently still lacking. Here, we report on the therapeutic efficacy of KH176, a new chemical entity derivative of Trolox, in Ndufs4 (-/-) mice, a mammalian model for Leigh Disease. Using in vivo brain diffusion tensor imaging, we show a loss of brain microstructural coherence in Ndufs4 (-/-) mice in the cerebral cortex, external capsule and cerebral peduncle. These findings are in line with the white matter diffusivity changes described in mitochondrial disease patients. Long-term KH176 treatment retained brain microstructural coherence in the external capsule in Ndufs4 (-/-) mice and normalized the increased lipid peroxidation in this area and the cerebral cortex. Furthermore, KH176 treatment was able to significantly improve rotarod and gait performance and reduced the degeneration of retinal ganglion cells in Ndufs4 (-/-) mice. These in vivo findings show that further development of KH176 as a potential treatment for mitochondrial disorders is worthwhile to pursue. Clinical trial studies to explore the potency, safety and efficacy of KH176 are ongoing

Delineating the mechanisms of cerebellar degeneration in paediatric and adult primary mitochondrial disease

\ua9 The Author(s) 2025.Cerebellar ataxia is a frequent, debilitating neurological manifestation of primary mitochondrial disease and is associated with extensive neurodegeneration of the cerebellar cortical circuitry. However, the precise neuropathological mechanisms resulting in cerebellar degeneration in paediatric and adult forms of mitochondrial disease remain unclear. We therefore sought to perform a comparative neuropathological study using post-mortem cerebellar tissues from 28 paediatric and adult patients with pathogenic bi-allelic POLG variants and pathogenic mitochondrial DNA variants (m.3243A > G, m.8344A > G, m.13094T > C, and m.14709T > C), in addition to 18 neurologically normal control cases. We also sought to assess the prevalence and progression of cerebellar ataxia in an adult mitochondrial disease patient clinical cohort (n = 310) harbouring the same pathogenic variants as the post-mortem cases. Analysis of the clinical patient cohort revealed that at least 23.5–39.7% of adult patients with primary mitochondrial disease had predominantly cerebellar ataxia, with disease progression evident in 38.8% of patients. In the mitochondrial disease post-mortem tissue cohort, there was clear evidence of selective loss of inhibitory Purkinje cells, with corresponding oxidative phosphorylation protein deficiencies, which were more severe in comparison to mainly excitatory neuronal populations of the granule cell layer and dentate nucleus. Remaining Purkinje cells also demonstrated an increased expression of mitophagy-related proteins, including LC3B and BNIP3. Focal necrotic cerebellar cortical lesions, identified in eight patients, were characterised by decreased parvalbumin immunoreactivity, and sporadic c-Fos immunoreactivity was observed throughout the cerebellar cortices of 14 patients, suggestive of cerebellar cortical hyperactivity. Overall, these neuropathological features were more severe in the early onset POLG-related disease group and patients who had epilepsy. Our findings provide an important insight to the pathological mechanisms contributing to the degeneration of the cerebellar cortex in paediatric and adult forms of primary mitochondrial disease, highlighting an increased burden of pathology in early onset POLG-related disease which may have important prognostic and therapeutic implications

The effects of warming on the ecophysiology of two co-existing kelp species with contrasting distributions

The northeast Atlantic has warmed significantly since the early 1980s, leading to shifts in species distributions and changes in the structure and functioning of communities and ecosystems. This study investigated the effects of increased temperature on two co-existing habitat-forming kelps: Laminaria digitata, a northern boreal species, and Laminaria ochroleuca, a southern Lusitanian species, to shed light on mechanisms underpinning responses of trailing and leading edge populations to warming. Kelp sporophytes collected from southwest United Kingdom were maintained under 3 treatments: ambient temperature (12 °C), +3 °C (15 °C) and +6 °C (18 °C) for 16 days. At higher temperatures, L. digitata showed a decline in growth rates and Fv/Fm, an increase in chemical defence production and a decrease in palatability. In contrast, L. ochroleuca demonstrated superior growth and photosynthesis at temperatures higher than current ambient levels, and was more heavily grazed. Whilst the observed decreased palatability of L. digitata held at higher temperatures could reduce top-down pressure on marginal populations, field observations of grazer densities suggest that this may be unimportant within the study system. Overall, our study suggests that shifts in trailing edge populations will be primarily driven by ecophysiological responses to high temperatures experienced during current and predicted thermal maxima, and although compensatory mechanisms may reduce top-down pressure on marginal populations, this is unlikely to be important within the current biogeographical context. Better understanding of the mechanisms underpinning climate-driven range shifts is important for habitat-forming species like kelps, which provide organic matter, create biogenic structure and alter environmental conditions for associated communities