Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

<p>Abstract</p> <p>Introduction</p> <p>Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations.</p> <p>Case presentation</p> <p>We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date.</p> <p>Conclusion</p> <p>It is therefore important to consider the diagnosis of Refsum disease in any patient with autosomal recessive or simplex retinitis pigmentosa, and to enquire about the presence of "unusual" feet or hands in such patients.</p

Managing concussion in the real world: Stakeholder perspectives of New Zealand Rugby's concussion management pathway

The potential adverse consequences associated with poor concussion management highlights the need to improve the translation of concussion guidelines into consistent use in real-world sport settings. To facilitate this process, New Zealand Rugby developed a community concussion management pathway to support concussion recognition, diagnosis, and management. This study adopted a pragmatic, descriptive qualitative approach to explore key stakeholders’ perceptions of the concussion management pathway, with the aim to inform policy and practice. Interviews were conducted with 123 participants, including players, parents, coaches, healthcare professionals, and school and provincial union representatives. The framework method was used to analyze data. Themes were organized according to the principles of realist process evaluation that considers contextual factors and mechanisms influencing a program's operation to produce specific outcomes. Contextual factors influencing the concussion management pathway's implementation included governing bodies’ support, existing local resources, general concussion attitudes, or concussion severity. The optimal functioning of the concussion management pathway (mechanism) was influenced by (i) pathway resources, (ii) roles and relationships, (iii) buy-in and support towards the concussion management pathway, and (iv) diligence and communication. Outcomes identified included (i) hitting the target (optimally managed and enhanced awareness) or (ii) missing the mark (dissatisfaction or management gaps). Overall, participants found the concussion management pathway valuable. However, the acceptability of certain policy-related aspects and the underlying attitudes associated with these perceptions, are some areas requiring further investigation and support. Tailoring programs according to end-users’ perceptions is crucial in developing context-sensitive interventions appropriate for a specific setting. These findings may act as a foundation for investigations of concussion management in other settings

Quest for clarity: investigating concussion-related responsibilities across the New Zealand Rugby Community System

There is a growing concern around concussions in rugby union, at all levels of the game. These concerns highlight the need to better manage and care for players. However, consistency around concussion-related responsibilities of stakeholders across the community rugby system remains challenging. Taking a systems thinking approach, this pragmatic, qualitative descriptive study explored key stakeholder groups within New Zealand’s community rugby system’s perceptions of their own and others’ concussion-related responsibilities. Participants included players from schools and clubs, coaches, parents, team leads and representatives from four provincial unions. A total of 155 participants (67 females and 88 males) were included in the study. Focus groups and individual interviews were conducted. Thematic content analysis was used to analyse data. Thirty concussion-related responsibilities were identified. These responsibilities were contained within four themes: (1) policies and support (responsibilities which influence policy, infrastructure, human or financial resources); (2) rugby culture and general management (responsibilities impacting players’ welfare and safety, attitudes and behaviour, including education, injury reporting and communication); (3) individual capabilities (responsibilities demonstrating knowledge and confidence managing concussion, leadership or role/task shifting) and (4) intervention following a suspected concussion (immediate responsibilities as a consequence of a suspected concussion). The need for role clarity was a prominent finding across themes. Additionally, injury management initiatives should prioritise communication between stakeholders and consider task-shifting opportunities for stakeholders with multiple responsibilities. How concussions will realistically be managed in a real-world sports setting and by whom needs to be clearly defined and accepted by each stakeholder group. A ‘framework of responsibilities’ may act as a starting point for discussion within different individual community rugby contexts on how these responsibilities translate to their context and how these responsibilities can be approached and assigned among available stakeholders

Plasma acylcarnitine concentrations reflect the acylcarnitine profile in cardiac tissues

Funding Information: This study was supported by the Latvian National Research Program BIOMEDICINE. E. Liepinsh was supported by the FP7 project InnovaBalt [grant Nr. 316149]. We would like to thank Dr. Reinis Vilskersts and Gita Dambrova for help with the isolated skeletal muscle experiments. Publisher Copyright: © 2017 The Author(s).Increased plasma concentrations of acylcarnitines (ACs) are suggested as a marker of metabolism disorders. The aim of the present study was to clarify which tissues are responsible for changes in the AC pool in plasma. The concentrations of medium- and long-chain ACs were changing during the fed-fast cycle in rat heart, muscles and liver. After 60 min running exercise, AC content was increased in fasted mice muscles, but not in plasma or heart. After glucose bolus administration in fasted rats, the AC concentrations in plasma decreased after 30 min but then began to increase, while in the muscles and liver, the contents of medium- and long-chain ACs were unchanged or even increased. Only the heart showed a decrease in medium- and long-chain AC contents that was similar to that observed in plasma. In isolated rat heart, but not isolated-contracting mice muscles, the significant efflux of medium- and long-chain ACs was observed. The efflux was reduced by 40% after the addition of glucose and insulin to the perfusion solution. Overall, these results indicate that during fed-fast cycle shifting the heart determines the medium- and long-chain AC profile in plasma, due to a rapid response to the availability of circulating energy substrates.publishersversionPeer reviewe

Insulin Sensitivity Is Reflected by Characteristic Metabolic Fingerprints - A Fourier Transform Mass Spectrometric Non-Targeted Metabolomics Approach

BACKGROUND: A decline in body insulin sensitivity in apparently healthy individuals indicates a high risk to develop type 2 diabetes. Investigating the metabolic fingerprints of individuals with different whole body insulin sensitivity according to the formula of Matsuda, et al. (ISI(Matsuda)) by a non-targeted metabolomics approach we aimed a) to figure out an unsuspicious and altered metabolic pattern, b) to estimate a threshold related to these changes based on the ISI, and c) to identify the metabolic pathways responsible for the discrimination of the two patterns. METHODOLOGY AND PRINCIPAL FINDINGS: By applying infusion ion cyclotron resonance Fourier transform mass spectrometry, we analyzed plasma of 46 non-diabetic subjects exhibiting high to low insulin sensitivities. The orthogonal partial least square model revealed a cluster of 28 individuals with alterations in their metabolic fingerprints associated with a decline in insulin sensitivity. This group could be separated from 18 subjects with an unsuspicious metabolite pattern. The orthogonal signal correction score scatter plot suggests a threshold of an ISI(Matsuda) of 15 for the discrimination of these two groups. Of note, a potential subgroup represented by eight individuals (ISI(Matsuda) value between 8.5 and 15) was identified in different models. This subgroup may indicate a metabolic transition state, since it is already located within the cluster of individuals with declined insulin sensitivity but the metabolic fingerprints still show some similarities with unaffected individuals (ISI >15). Moreover, the highest number of metabolite intensity differences between unsuspicious and altered metabolic fingerprints was detected in lipid metabolic pathways (arachidonic acid metabolism, metabolism of essential fatty acids and biosynthesis of unsaturated fatty acids), steroid hormone biosyntheses and bile acid metabolism, based on data evaluation using the metabolic annotation interface MassTRIX. CONCLUSIONS: Our results suggest that altered metabolite patterns that reflect changes in insulin sensitivity respectively the ISI(Matsuda) are dominated by lipid-related pathways. Furthermore, a metabolic transition state reflected by heterogeneous metabolite fingerprints may precede severe alterations of metabolism. Our findings offer future prospects for novel insights in the pathogenesis of the pre-diabetic phase

Medium Chain Acylcarnitines Dominate the Metabolite Pattern in Humans under Moderate Intensity Exercise and Support Lipid Oxidation

Background: Exercise is an extreme physiological challenge for skeletal muscle energy metabolism and has notable health benefits. We aimed to identify and characterize metabolites, which are components of the regulatory network mediating the beneficial metabolic adaptation to exercise

Metabolic changes in concussed American football players during the acute and chronic post-injury phases

<p>Abstract</p> <p>Background</p> <p>Despite negative neuroimaging findings many athletes display neurophysiological alterations and post-concussion symptoms that may be attributable to neurometabolic alterations.</p> <p>Methods</p> <p>The present study investigated the effects of sports concussion on brain metabolism using ¹H-MR Spectroscopy by comparing a group of 10 non-concussed athletes with a group of 10 concussed athletes of the same age (mean: 22.5 years) and education (mean: 16 years) within both the acute and chronic post-injury phases. All athletes were scanned 1-6 days post-concussion and again 6-months later in a 3T Siemens MRI.</p> <p>Results</p> <p>Concussed athletes demonstrated neurometabolic impairment in prefrontal and motor (M1) cortices in the acute phase where NAA:Cr levels remained depressed relative to controls. There was some recovery observed in the chronic phase where Glu:Cr levels returned to those of control athletes; however, there was a pathological increase of m-I:Cr levels in M1 that was only present in the chronic phase.</p> <p>Conclusions</p> <p>These results confirm cortical neurometabolic changes in the acute post-concussion phase as well as recovery and continued metabolic abnormalities in the chronic phase. The results indicate that complex pathophysiological processes differ depending on the post-injury phase and the neurometabolite in question.</p