Development of MRC Centre MRI calf muscle fat fraction protocol as a sensitive outcome measure in Hereditary Sensory Neuropathy Type 1
Umaiyal KugathasanMatthew R. EvansJasper M. MorrowChristopher D. J. SinclairJohn S. ThorntonTarek YousryThorsten HornemannSaranya SuriyanarayananKhadijah Owusu-AnsahGiuseppe LauriaRaffaella LombardiJames M. PolkeEmma R. WilsonDavid BennettHenry HouldenMichael G. HannaJulian BlakeMatilde LauráMary M. Reilly
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Hereditary sensory neuropathy type 1 (HSN1) is a rare, slowly progressive neuropathy causing profound sensory deficits and often severe motor loss. L-serine supplementation is a possible candidate therapy but the lack of responsive outcome measures is a barrier for undertaking clinical trials in HSN1. We performed a 12-month natural history study to characterise the phenotype of HSN1 and to identify responsive outcome measures.Assessments included Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), CMTNSv2-Rasch modified, nerve conduction studies, quantitative sensory testing, intraepidermal nerve fibre density (thigh), computerised myometry (lower limbs), plasma 1-deoxysphingolipid levels, calf-level intramuscular fat accumulation by MRI and patient-based questionnaires (Neuropathic Pain Symptom Inventory and 36-Short Form Health Survey version 2 [SF-36v2]).35 patients with HSN1 were recruited. There was marked heterogeneity in the phenotype mainly due to differences between the sexes: males generally more severely affected. The outcome measures that significantly changed over 1 year and correlated with CMTNSv2, SF-36v2-physical component and disease duration were MRI determined calf intramuscular fat accumulation (mean change in overall calf fat fraction 2.36%, 95% CI 1.16 to 3.55, p=0.0004), pressure pain threshold on the hand (mean change 40 kPa, 95% CI 0.7 to 80, p=0.046) and myometric measurements of ankle plantar flexion (median change -0.5 Nm, IQR -9.5 to 0, p=0.0007), ankle inversion (mean change -0.89 Nm, 95% CI -1.66 to -0.12, p=0.03) and eversion (mean change -1.61 Nm, 95% CI -2.72 to -0.51, p=0.006). Intramuscular calf fat fraction was the most responsive outcome measure.MRI determined calf muscle fat fraction shows validity and high responsiveness over 12 months and will be useful in HSN1 clinical trials.Keywords:
Intramuscular fat
Intramuscular fat(IMF) content is one of major determinants of pork quality.Intramuscular fat affects pork quality by flavor,juiceness and muscle tenderness,and so on.Therefore,it' s an effective way to improve meat quality by altering the content of intramuscular fat.The deposition of intramuscular fat can be regulated by many factors such as gene,nutrition,environment,and so on,in which the factors of gene and nutrition are often researched,in the contrary to the effect of environment and sex which have a certain extent effect on deposition of intramuscular fat.In this article,the advance in the research of regulation of intramuscular fat for commercial pigs was summarized for higher quality pork and guiding the production.
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1) To determine if the neuropathic pain scale (NPS) can be used to classify chronic pain patients (CPPs) as having primarily neuropathic vs non-neuropathic pain, and furthermore; 2) to determine what, if any, cut-off score can be used to reliably make this determination.A total of 305 CPPs consecutive admissions to The Rosomoff Pain Center were administered the NPS and were assigned a diagnosis according to the physical examination and all available test results. CPPs with a diagnosis of chronic radiculopathy and spondylolysis/degenerative arthritis were segregated into two groups for the purposes of having a group representative of neuropathic pain (chronic radiculopathy) and non-neuropathic pain (spondylolysis/degenerative arthritis). Applying neuropathic pain criteria to each "of these two groups": a neuropathic pain "subtype" was identified within the chronic radiculopathy group; and, a non-neuropathic pain "subtype" was identified within the spondylolysis/degenerative arthritis group. This step was performed in order to assure that the CPPs selected for further analysis were truly representative of neuropathic and non-neuropathic pain. Discriminant function analysis was then employed to determine if NPS scoring could differentiate between these two "subtypes." Results from the discriminant function analysis model were utilized to derive an NPS cut-off score above which CPPs would be classified as having neuropathic pain. For the diagnoses of myofascial pain syndromes, spinal stenosis, epidural fibrosis, fibromyalgia, complex regional pain syndromes 1 and 2, and failed back surgery syndrome, a predicted NPS score was calculated and compared with the cut-off score.Multidisciplinary pain facility.Chronic pain patients.The NPS appeared to be able to separate CPPs into neuropathic pain vs non-neuropathic pain subtypes. The derived cut-off score from the model was 5.53. Myofascial pain syndrome and spinal stenosis had predictive scores lower than this cut-off score at 3.81 and 4.26, respectively. Epidural fibrosis, fibromyalgia, complex regional pain syndromes 1 and 2, and failed back surgery syndrome had predictive scores higher than the cut-off score at 6.15, 6.35, 6.87, 9.34, and 7.19, respectively.The NPS appears to be able to discriminate between neuropathic and non-neuropathic pain. A debate is currently raging as to whether diagnoses, such as fibromyalgia and complex regional pain syndrome 1, can be classified as neuropathic. Our NPS cut-off score results suggest that these diagnoses may have a neuropathic pain component. The reliability and validity of our NPS method will need to be tested further in other neuropathic pain models, such as diabetic peripheral neuropathic pain.
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We aimed to evaluate the performance, carcass and pork quality traits, as well as the mRNA expression of genes related to intramuscular fat deposition in female pigs from different genetic lines. A total of eighteen female pigs (Large White × Landrace × Duroc × Pietrain) × (Large White × Landrace) (Hybrid) averaging 88.96 ± 3.44 kg in body weight and twelve female pigs (Duroc) × (Large White × Landrace) (Duroc) averaging 85.63 ± 1.55 kg in body weight were assigned to a completely randomized design experimental trial that lasted 45 days. Pigs from both genetic lines received the same diet, which was initially adjusted for their nutritional requirements from 0 to 17 days of age and subsequently adjusted for nutritional requirements from 17 to 45 days of age. The performance of pigs did not differ among groups (p > 0.05). Duroc pigs showed a lower backfat thickness (p < 0.03) and greater intramuscular fat content (p < 0.1). A greater mRNA expression of the peroxisome proliferator-activated receptor gamma gene (PPARγ, p = 0.008) and fatty acid protein translocase/cluster differentiation (FAT/CD36, p = 0.002) was observed in the Longissimus dorsi muscle of Duroc pigs. Similarly, a greater expression of PPARγ (p = 0.009) and FAT/CD36 (p = 0.02) was observed in the Soleus muscle of Duroc pigs. Overall, we observed that despite the lack of differences in performance between the genetic groups, Duroc pigs had greater intramuscular fat content than hybrid pigs. The increased intramuscular fat content was associated with an increase in the mRNA expression of key transcriptional factors and genes encoding enzymes involved in adipogenesis and lipogenesis in glycolytic and oxidative skeletal muscle tissues.
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Background Despite the suggestion of a neuropathic component to sickle cell disease (SCD) pain, there are minimal data on the systematic assessment of neuropathic pain in patients with SCD. Neuropathic pain is defined as pain primarily initiated by dysfunction of the peripheral or central nervous system. Procedure In a cross-sectional study, we used the painDETECT questionnaire, a one-page validated neuropathic pain screening tool, to determine the presence of neuropathic pain in patients with SCD and to evaluate the relationship between neuropathic pain, age, and gender. We hypothesized that 20% of patients with SCD will experience neuropathic pain and that neuropathic pain will be associated with older age and female gender. The completed painDETECT questionnaire yields a total score between 0 and 38 (≥19 = definite neuropathic pain, 13–18 = probable neuropathic pain, ≤12 = no neuropathic pain). Scores ≥13 were designated as having evidence of neuropathic pain. Results A total of 56 patients participated. Median age was 20.3 years and 77% were female. We found 37% of patients had evidence of neuropathic pain. Age was positively correlated with total score (r = 0.43; P = 0.001) suggesting older patients experience more neuropathic pain. Females had higher mean total scores (13 vs. 8.4; P = 0.04). Significantly more patients with neuropathic pain were taking hydroxyurea (90% vs. 59%; P = 0.015). Despite 37% of patients experiencing neuropathic pain, only 5% were taking a neuropathic pain drug. Conclusions Neuropathic pain exists in SCD. Valid screening tools can identify patients that would benefit from existing and future neuropathic pain therapies and could determine the impact of these therapies. Pediatr Blood Cancer 2014;61:512–517. © 2013 Wiley Periodicals, Inc.
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Intramuscular fat content is an important factor to influence beef quality,which directly affects the meat tenderness and flavor. The beef intramuscular fat deposition- related functional genes are briefly reviewed in this paper,which provides a reference for deeply studying these functional genes by increasing intramuscular fat content to improve beef quality.
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Intramuscular fat content and distribution (marbling) are important attributes for beef quality grading. The USDA (United States Department of Agriculture) certified inspectors determine the beef quality grades, based on marbling, by visually inspecting the cross sections of longissimus dorsi (ribeye) muscle at the 12th rib location on chilled beef carcass. This subjective method of grading, however, will not meet the meat industry's demand for a value based marketing system. One important step towards this goal is an objective method of characterizing intramuscular fat or marbling. B-mode ultrasound has been shown to have the potential for predicting intramuscular percentage fat (%-fat) in live animals [1] as well as carcasses [2]. This paper presents the potential of A-mode ultrasound for characterizing intramuscular fat.
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Genetic parameters such as heritability and correlations of fat traits in a Duroc population were dissected using molecular markers. The heritabilities of intramuscular fat in 2 muscles, the gluteus medius and LM, and back fat were 0.54, 0.48, and 0.23, respectively. The genetic correlations were well estimated with standardized SNP effects, being 0.65 between intramuscular fat traits and ∼0.37 between any intramuscular fat trait and back fat. Genetic correlations were overestimated when ignoring molecular information. Twelve chromosomes showed additive genetic variance for intramuscular fat compared with 8 for back fat. Population structure was accommodated using 4 different models. The number of significant, P < 5 × 10(-5) (suggestive, P < 2 × 10(-3)), SNP varied across models and ranged from 0 to 4 (2 to 261) for intramuscular fat in the gluteus medius, from 0 to 57 (9 to 564) for intramuscular fat in the LM, and from 3 to 4 (22 to 168) for back fat. Several SNP showed significant deviations from an additive mode of action. Only 2 SNP significantly affected 2 traits simultaneously.
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Summary Marbling, as defined by the amount of intramuscular fat, is an economically important trait in beef cattle. Intramuscular fat deposition is postulated to arise mainly from a series of adipogenic events in intramuscular adipocyte‐lineage cells and in the physiological or anatomical milieux surrounding them. This study was designed to investigate gene‐expression patterns associated with fat deposition in musculus longissimus muscle, including adipocyte‐lineage cells and part of the milieux. Differential‐display PCR (ddPCR) was used to examine expression differences between low‐marbled and high‐marbled steer groups at 8, 10, 12 and 14 months of age, encompassing the time that marbling starts to appear. Seventy‐four of 2114 total bands on ddPCR gel‐bands were significant ( P < 0.05) for the group effect, the interaction effect between group and age, or both the group and the interaction effects. Sequence analysis of 72 of these bands revealed 77 genes, including 35 annotated genes and 42 novel sequences. Among the 35 annotated genes, 6 ( BTG2 , PDHB , SORBS1 , TRDN , TTN and MGP ) have been related to changes in intramuscular fat deposition, possibly by exerting effects on adipocyte‐lineage cells or on the milieux surrounding them.
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