3D 7Li magnetic resonance imaging of brain lithium distribution in bipolar disorder

Lithium is a major treatment for bipolar disorder and the likelihood of a favourable response may be determined by its distribution in the brain. Lithium can be directly detected by magnetic resonance (MR), but previous 7Li MR spectroscopy studies have demonstrated that this is challenging compared to conventional 1H MR imaging due to the MR properties of the lithium nucleus and its low concentration in brain tissue, as dictated by therapeutic dose. We have tested and implemented a highly efficient balanced steady-state free precession 7Li-MRI method to address these challenges and enable MRI of brain lithium in a short duration scan. We report a 3D 7Li-MRI acquisition with 25 mm isotropic resolution in an 8-min scan that demonstrates heterogeneity in lithium concentration within the brain in subjects with bipolar disorder. This represents the direct imaging of a pharmaceutical agent in its target organ and notably expands the repertoire of techniques available to investigate the effects of lithium in man

Emotions in context: examining pervasive affective sensing systems, applications, and analyses

Pervasive sensing has opened up new opportunities for measuring our feelings and understanding our behavior by monitoring our affective states while mobile. This review paper surveys pervasive affect sensing by examining and considering three major elements of affective pervasive systems, namely; “sensing”, “analysis”, and “application”. Sensing investigates the different sensing modalities that are used in existing real-time affective applications, Analysis explores different approaches to emotion recognition and visualization based on different types of collected data, and Application investigates different leading areas of affective applications. For each of the three aspects, the paper includes an extensive survey of the literature and finally outlines some of challenges and future research opportunities of affective sensing in the context of pervasive computing

In Vivo Magnetic Resonance Studies of Glycine and Glutathione Metabolism in a Rat Mammary Tumor

The metabolism of glycine into glutathione was monitored noninvasively in vivo in intact R3230Ac rat tumors by magnetic resonance imaging and spectroscopy. Metabolism was tracked by following the isotope label from intravenously infused [2-13C]-glycine into the glycinyl residue of glutathione. Signals from [2-13C]-glycine and γ-glutamylcysteinyl-[2-13C]-glycine (13C-glutathione) were detected by nonlocalized 13C spectroscopy as these resonances are distinct from background signals. In addition, using spectroscopic imaging methods, heterogeneity in the in vivo tumor distribution of glutathione was observed. In vivo spectroscopy also detected isotope incorporation from [2-13C]-glycine into both the 2- and 3-carbons of serine. Analyses of tumor tissue extracts show single and multiple label incorporation from [2-13C]-glycine into serine from metabolism through the serine hydroxymethyltransferase and glycine cleavage system pathways. Mass spectrometric analysis of extracts also shows that isotope-labeled serine is further metabolized via the transsulfuration pathway as the 13C-isotope labels appear in both the glycinyl- and the cysteinyl-residue of glutathione. Our studies demonstrate the use of magnetic resonance imaging and spectroscopy for monitoring tumor metabolic processes central to oxidative stress defense

Inhibition of lipolysis in Type 2 diabetes normalizes glucose disposal without change in muscle glycogen synthesis rates

Suppression of lipolysis by acipimox is known to improve insulin-stimulated glucose disposal, and this is an important phenomenon. The mechanism has been assumed to be an enhancement of glucose storage as glycogen, but no direct measurement has tested this concept or its possible relationship to the reported impairment in insulin-stimulated muscle ATP production. Isoglycaemic–hyperinsulinaemic clamps with [13C]glucose infusion were performed on Type 2 diabetic subjects and matched controls with measurement of glycogen synthesis by 13C MRS (magnetic resonance spectroscopy) of muscle. 31P saturation transfer MRS was used to quantify muscle ATP turnover rates. Glucose disposal rates were restored to near normal in diabetic subjects after acipimox (6.2±0.8 compared with 4.8±0.6 mg·kgffm−1·min−1; P<0.01; control 6.6±0.5 mg·kgffm−1·min−1; where ffm, is fat-free mass). The increment in muscle glycogen concentration was 2-fold higher in controls compared with the diabetic group, and acipimox administration to the diabetic group did not increase this (2.0±0.8 compared with 1.9±1.1 mmol/l; P<0.05; control, 4.0±0.8 mmol/l). ATP turnover rates did not increase during insulin stimulation in any group, but a modest decrease in the diabetes group was prevented by lowering plasma NEFAs (non-esterified fatty acids; 8.4±0.7 compared with 7.1±0.5 μmol·g−1·min−1; P<0.05; controls 8.6±0.8 μmol·g−1·min−1). Suppression of lipolysis increases whole-body glucose uptake with no increase in the rate of glucose storage as glycogen but with increase in whole-body glucose oxidation rate. ATP turnover rate in muscle exhibits no relationship to the acute metabolic effect of insulin

Identification of research communities in cited and uncited publications using a co-authorship network

Patterns of co-authorship provide an effective means of probing the structures of research communities. In this paper, we use the CiteSpace social network tool and co-authorship data from the Web of Science to analyse two such types of community. The first type is based on the cited publications of a group of highly productive authors in a particular discipline, and the second on the uncited publications of those highly productive authors. These pairs of communities were generated for three different countries—the People’s Republic of China (PRC), the United Kingdom (UK) and the United States of America (USA)—and for four different disciplines (as denoted by Web of Science subject categories)—Chemistry Organic, Engineering Environmental, Economics, and Management. In the case of the UK and USA, the structures of the cited and uncited communities in each of the four disciplines were markedly different from each other; in the case of the PRC, conversely, the cited and uncited PRC communities had broadly similar structures that were characterised by large groups of connected authors. We suggest that this may arise from a greater degree of guest or honorary authorship in the PRC than in the UK or the USA

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Human brain ⁷Li-MRI following low-dose lithium dietary supplementation in healthy participants

Background: Lithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging (7Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose. Methods: Lithium orotate supplements were taken by nine healthy adult male subjects (5 mg daily) for up to 28 days, providing 2–7 % of the lithium content of a typical therapeutic lithium carbonate dose. One-dimensional 7Li-images were acquired on a 3.0 T MRI scanner. All subjects were scanned on day 14 or 28; seven were scanned on both, one at baseline and one after 7-days washout. Results: 7Li-MR signal amplitude was broadly stable between days 14 and 28. Two subjects had notably higher 7Li-signal intensities (approximately 2–4×) compared to other study participants. Limitations: Lithium adherence was self-reported by all participants without formal validation. The coarse spatial resolution necessary for detection of low concentrations of 7Li exhibits imperfect spatial separation of signal from adjacent pixels. Conclusions: 7Li-MRI performed using a clinical 3T scanner demonstrated detection of lithium in the brain at very low concentration, in the range of approximately 10–60 mM. The methods are suited to studies assessing low dose lithium administration in psychiatric and neurodegenerative disorders, and permit the comparison of different lithium salt preparations at a time of emerging interest in the field.</p