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Background: Phosphorus cardiovascular magnetic resonance spectroscopy (31P-CMRS) has emerged as an important tool for the preclinical assessment of myocardial energetics in vivo. However, the high rate and diminutive size of the mouse heart is a challenge, resulting in low resolution and poor signal-to-noise. Here we describe a refined high-resolution 31P-CMRS technique and apply it to a novel double transgenic mouse (dTg) with elevated myocardial creatine and creatine kinase (CK) activity. We hypothesised a synergistic effect to augment energetic status, evidenced by an increase in the ratio of phosphocreatine-to-adenosine-triphosphate (PCr/ATP). Methods and results: Single transgenic Creatine Transporter overexpressing (CrT-OE, n = 7) and dTg mice (CrT-OE and CK, n = 6) mice were anaesthetised with isoflurane to acquire 31P-CMRS measurements of the left ventricle (LV) utilising a two-dimensional (2D), threefold under-sampled density-weighted chemical shift imaging (2D-CSI) sequence, which provided high-resolution data with nominal voxel size of 8.5 µl within 70 min. (1H-) cine-CMR data for cardiac function assessment were obtained in the same imaging session. Under a separate examination, mice received invasive haemodynamic assessment, after which tissue was collected for biochemical analysis. Myocardial creatine levels were elevated in all mouse hearts, but only dTg exhibited significantly elevated CK activity, resulting in a 51% higher PCr/ATP ratio in heart (3.01 ± 0.96 vs. 2.04 ± 0.57—mean ± SD; dTg vs. CrT-OE), that was absent from adjacent skeletal muscle. No significant differences were observed for any parameters of LV structure and function, confirming that augmentation of CK activity does not have unforeseen consequences for the heart. Conclusions: We have developed an improved 31P-CMRS methodology for the in vivo assessment of energetics in the murine heart which enabled high-resolution imaging within acceptable scan times. Mice over-expressing both creatine and CK in the heart exhibited a synergistic elevation in PCr/ATP that can now be tested for therapeutic potential in models of chronic heart failure. [ABSTRACT FROM AUTHOR]

Aims: Low levels of homoarginine and creatine are associated with heart failure severity in humans, but it is unclear to what extent they contribute to pathophysiology. Both are synthesized via L‐arginine:glycine amidinotransferase (AGAT), such that AGAT−/− mice have a combined creatine and homoarginine deficiency. We hypothesized that this would be detrimental in the setting of chronic heart failure. Methods and results: Study 1: homoarginine deficiency—female AGAT−/− and wild‐type mice were given creatine‐supplemented diet so that both had normal myocardial creatine levels, but only AGAT−/− had low plasma homoarginine. Myocardial infarction (MI) was surgically induced and left ventricular (LV) structure and function assessed at 6–7 weeks by in vivo imaging and haemodynamics. Study 2: homoarginine and creatine‐deficiency—as before, but AGAT−/− mice were given creatine‐supplemented diet until 1 week post‐MI, when 50% were changed to a creatine‐free diet. Both groups therefore had low homoarginine levels, but one group also developed lower myocardial creatine levels. In both studies, all groups had LV remodelling and dysfunction commensurate with the development of chronic heart failure, for example, LV dilatation and mean ejection fraction <20%. However, neither homoarginine deficiency alone or in combination with creatine deficiency had a significant effect on mortality, LV remodelling, or on any indices of contractile and lusitropic function. Conclusions: Low levels of homoarginine and creatine do not worsen chronic heart failure arguing against a major causative role in disease progression. This suggests that it is unnecessary to correct hArg deficiency in patients with heart failure, although supra‐physiological levels may still be beneficial. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the impact of surgical debridement on the microbiology of resection margins of an infected diabetic foot ulcer and to compare the use of marginal sampling as a guide for antimicrobial therapy. Methods: Forty consecutive participants were studied. Tissue samples from infected diabetic foot ulcers were obtained at first contact by podiatrists. After surgical debridement to macroscopically healthy tissue, multiple samples were obtained from the margins of the residuum and also from excised non‐viable tissue. Debridement was done by a single surgeon. Bacterial species were classified according to pathogenic potential a priori into Red Group—Definite pathogen causing infection, Yellow Group—Likely to be causing infection if present in more than one specimen and Green Group –Commensals, not causing infection. Results: There was a relative reduction of 49% (p = 0.002) in bacteria in the most pathogenic (red) group, and 59% (p = 0.002) in the yellow group in podiatry samples compared with resection specimen. Positive cultures from margins of the residuum were observed in 75% of cases. There was a relative reduction of 67% (p = 0.0001) in bacteria in the red and 48% (p = 0.06) in the yellow group in marginal samples from the residuum compared with podiatry samples. Conclusions: After surgical debridement to healthy tissue, positive cultures from marginal tissue samples provided vital information on the presence of pathogenic bacteria. This allowed antibiotics to be individualised post‐surgical debridement. [ABSTRACT FROM AUTHOR]

Objectives: The differential diagnosis of psychotic symptoms is broad and extends beyond primary psychotic and affective disorders. We aim to illustrate that the chronology and phenomenological nature of hallucinatory symptoms may provide clues towards alternative diagnoses, such as hallucinogen persisting perceptual disorder (HPPD). We describe the resurgence of visual pseudo-hallucinations in a young woman in the context of previous substance-induced hallucinatory symptoms and a prior diagnosis of occipital lobe epilepsy. She presented a diagnostic challenge, saw several emergency and specialist doctors and attracted stigmatising diagnoses leading to anxiety and depressive symptoms. Her symptoms were finally recognised as HPPD, and she was treated appropriately with lamotrigine.Conclusions: Patients with perceptual disturbance can present in various clinical settings, and HPPD is an under-recognised diagnostic possibility. Delayed or misdiagnosis prolongs profound functional impairment and social decline, and predisposes the patient to the development of anxiety and depression and related increased risk of suicide. [ABSTRACT FROM AUTHOR]