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Background and Aims: Gastrointestinal (GI) dysmotility is a common and debilitating clinical manifestation in patients with mitochondrial DNA (mtDNA)–related disease with no curative and few effective symptomatic therapies. A low-residue diet (LRD) has been shown to be effective at reducing bowel urgency, pain, and distension in functional GI-related conditions. We assessed tolerability and effects of an LRD on bowel habits in patients with mtDNA-related disease. Methods: This was a 12-week single-arm pilot study in patients with genetically determined primary mtDNA-related disease, meeting the ROME III constipation criteria. The co-primary outcomes were tolerability of an LRD (

Background: Age-associated decline in physiological function has been identified as the main factor increasing disease risk, including cardiovascular (CVD) and gastrointestinal tract (GIT) diseases. Nutritional interventions encompassing dietary inorganic nitrates, such as nitrate rich beetroot may reduce the risk for CVD and GIT. Objective: Assess the impact of whole beetroot on blood pressure (BP), microbiota profile and functional measures (physical and bowel). Design: Thirty-six healthy participants were recruited (mean age 67 ± 6 years; body mass index (BMI) 25 ± 2 kg/m2) and assigned randomly to a beetroot (n = 19) or control group (n = 17). Beetroot group consumed 150 g of whole beetroot and a medium-sized banana and the control group consumed a medium-sized banana every second day for 8 weeks. Resting BP, microbiota profiling, physical activity, urinary nitrate, short-chain fatty acids (SCFA) and Bristol Stool Score (BSS) were measured at 0, 4 and 8 weeks. Plasma nitrate was measured at weeks 0 and 8. Results: The beetroot group had a resting systolic BP reduction of 8.0 mmHg (p = 0.03), lower relative abundance of the phyla Bacteroidetes (p = 0.04), and a higher relative abundance of genus Alistipes (p = 0.03), increased Shannon diversity index (p = 0.03), fibre intake of 7 g/day (p

Abstract Objectives Defining clinically relevant outcome measures for myotonic dystrophy type 1 (DM1) that can be valid and feasible for different phenotypes has proven problematic. The Outcome Measures for Myotonic Dystrophy (OMMYD) group proposed a battery of functional outcomes: 6‐minute walk test, 30 seconds sit and stand test, timed 10 m walk test, timed 10 m walk/run test, and nine‐hole peg test. This, however, required a large‐scale investigation, Methods A cohort of 213 patients enrolled in the natural history study, PhenoDM1, was analyzed in cross‐sectional analysis and subsequently 98 patients were followed for longitudinal analysis. We aimed to assess: (1) feasibility and best practice; (2) intra‐session reliability; (3) validity; and (4) behavior over time, of these tests. Results OMMYD outcomes proved feasible as 96% of the participants completed at least one trial for all tests and more than half (n = 113) performed all three trials of each test. Body mass index and disease severity associate with functional capacity. There was a significant difference between the first and second trials of each test. There was a moderate to strong correlation between these functional outcomes and muscle strength, disease severity and patient‐reported outcomes. All outcomes after 1 year detected a change in functional capacity except the nine‐hole peg test. Conclusions These tests can be used as a battery of outcomes or independently based on the shown overlapping psychometric features and strong cross‐correlations. Due to the large and heterogeneous sample of this study, these results can serve as reference values for future studies.

Abstract Objective To determine the cognitive profile of adult patients with mitochondrial disease, and the effect of disease severity on cognition. Methods Using a prospective case‐control design, we compared cognition of patients to normative data and to matched controls, assessed three times over 18 months. Forty‐nine patients with m.3243A>G (N = 36) and m.8344A>G (N = 13) mtDNA mutations and 32 controls, matched by age (±5 years) and premorbid cognition (±10 WTAR FSIQ points), participated. Participants completed neuropsychological assessments of general cognition (WAIS‐IV), executive function (D‐KEFS), and memory (WMS‐IV). Potential predictors of cognition were explored. Results Patients show mild‐to‐moderate premorbid cognitive impairment, but substantial impairment in current general cognition and distinct domains, including verbal comprehension, perceptual reasoning, working memory, processing speed, and memory retrieval. Executive dysfunction may be caused by slower decision‐making. Patients performed worse than controls, except on memory tasks, indicating intact memory, when premorbid cognition is controlled for. Premorbid cognition and disease severity were consistent predictors of cognition in patients; however, cognitive decline appears slow and is unlikely in the short‐term, when other disease‐specific factors remain stable. Interpretation Patients should be monitored to facilitate early identification of a complex profile of cognitive deficits and individuals with higher disease burden should be followed up more closely. On development of cognitive difficulties, appropriate compensatory strategies should be determined through in‐depth assessment. Using strategies such as slower presentation of information, multiple modes of presentation, active discussion to aid understanding and decision‐making, and use of memory aids, may ameliorate difficulties.

Abstract Background With over 800 million cases globally, campylobacteriosis is a major cause of food borne disease. In temperate climates incidence is highly seasonal but the underlying mechanisms are poorly understood, making human disease control difficult. We hypothesised that observed disease patterns reflect complex interactions between weather, patterns of human risk behaviour, immune status and level of food contamination. Only by understanding these can we find effective interventions. Methods We analysed trends in human Campylobacter cases in NE England from 2004 to 2009, investigating the associations between different risk factors and disease using time-series models. We then developed an individual-based (IB) model of risk behaviour, human immunological responses to infection and environmental contamination driven by weather and land use. We parameterised the IB model for NE England and compared outputs to observed numbers of reported cases each month in the population in 2004–2009. Finally, we used it to investigate different community level disease reduction strategies. Results Risk behaviours like countryside visits (t = 3.665, P

Mitochondrial respiratory chain deficiency and mitochondrial DNA deletions are reported in substantia nigra neurons from healthy aged and Parkinson's disease cases, with extensive neuronal loss only seen in the latter. This study aimed to understand the pathological relevance of mitochondrial defects for neuronal survival. Using post-mortem human midbrain, substantia nigra neurons exposed to different types of mitochondrial defects (including mitochondrial DNA point mutations, single and multiple deletions) were compared to neurons from healthy aged and Parkinson's disease cases (either sex) at a single neuronal level. We identified mitochondrial deficiencies in all cases, though these deficiencies were more severe in the mitochondrial disease patients with multiple deletions. A significant reduction in TFAM expression was detected in Parkinson's disease compared to cases with other mitochondrial defects. Higher mitochondrial DNA copy number was detected in healthy aged neurons, despite a deletion level equivalent to Parkinson's disease. Our data support that in individuals with pathogenic mitochondrial defects, neurons respond to mitochondrial defect to survive and such an adaptation may involve TFAM.