Aagaardkrebs6953

Glycogen storage disease type V (GSDV) is a rare inborn error of carbohydrate metabolism. Patients present with exercise intolerance due to blocked glycogen breakdown in skeletal muscle. Introducing alternative fuel substrates, such as ketone bodies (KBs), could potentially alleviate muscle symptoms. This pilot study investigates which of three different modified ketogenic diet regimes is optimal for GSDV-patients to follow in a future large-scale study. Participants were randomised to follow one of three diet regimes for 3 weeks (#1 65%/15%/20%; #2 75%/15%/10%, or #3 80%/15%/5%, fat/protein/carbohydrate). The primary outcome was exercise tolerance assessed by heart rate (HR) changes during constant load cycling. Secondary outcomes included levels of ketosis, and changes in perceived exertion and indirect calorimetry measures during exercise. Ten GSDV-patients were included. Eight completed the study. The other two were excluded. Diet #3 showed the highest average KB level (1.1 mmol/L) vs #2 (0.5 mmol/L) and #1 (0.3 mmol/L). Five patients reported subjective symptom relief, all of whom were on diets #2 and #3. All diet regimes seemed to improve fatty acid oxidation rates and exercise capacity as indicated by a small decrease in HR and perceived exertion. The results of this open-label pilot study show that diets #2 and #3 induce ketosis and improve symptoms and exercise capacity in GSDV-patients. Diet #2 had the highest acceptability score and was superior or equal to diet #3 in all other parameters, except level of ketosis. Based on this, we suggest testing diet #2 in a large-scale, placebo-controlled study in GSDV. © 2020 SSIEM.Imipenem-cilastatin-relebactam (IMI-REL) is a novel β-lactam-β-lactamase inhibitor combination recently approved for the treatment of complicated urinary tract infections (cUTIs) and complicated intraabdominal infections (cIAIs). Relebactam is a β-lactamase inhibitor with the ability to inhibit a broad spectrum of β-lactamases such as class A and class C β-lactamases, including carbapenemases. The addition of relebactam to imipenem restores imipenem activity against several imipenem-resistant bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa. Clinical data demonstrate that IMI-REL is well tolerated and effective in the treatment of cUTIs and cIAIs due to imipenem-resistant bacteria. In a phase III trial comparing IMI-REL with imipenem plus colistin, favorable clinical response was achieved in 71% and 70% of patients, respectively. Available clinical and pharmacokinetic data support the approved dosage of a 30-minute infusion of imipenem 500 mg-cilastatin 500 mg-relebactam 250 mg every 6 hours, along with dosage adjustments based on renal function. In this review, we describe the chemistry, mechanism of action, spectrum of activity, pharmacokinetics and pharmacodynamics, and clinical efficacy, and safety and tolerability of this new agent. The approval of IMI-REL represents another important step in the ongoing fight against multidrug-resistant gram-negative pathogens. © 2020 Pharmacotherapy Publications, Inc.PURPOSE It may be challenging to select the optimal scan duration for single-photon emission computed tomography (SPECT) protocols because the activity distribution characteristics can differ in every scan. Using simulations and experiments, we investigated whether the scan duration can be optimized for every scan separately by evaluating the activity distribution during scanning. We refer to this as adaptive scanning. METHODS The feasibility of adaptive scanning was evaluated for the detection of extrahepatic depositions in the pretreatment procedure of radioembolization, in which 99m Tc-labeled macroaggregated albumin (99m Tc-MAA) is injected into the liver. We simulated fast 1-min detector rotations and updated the reconstruction with the newly collected counts after every rotation. The scan was terminated when one of the two criteria was met (a) when the mask difference of the detected extrahepatic deposition between two consecutive rotations was lower than 5%; or (b) when the reconstructed extrahepatic ay 7.0 ± 1.0%. CONCLUSION Our study suggests that the SPECT scan duration can be personalized by assessing the activity distribution characteristics during scanning for the detection of extrahepatic depositions in the pretreatment procedure of radioembolization. The adaptive scanning approach might also be of benefit for other SPECT protocols, as long as a measure of interest is available for optimization. © 2020 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.Boldness and risk-taking behaviours in animals are important traits to obtain advantages such as habitation, food resources, reproductive success and social dominance. Risk-taking behaviour is influenced by physiological and environmental conditions; however, whether individual fish become bolder by the presence of conspecifics remains unknown. In this study, a light-dark preference test was conducted using medaka fish (Oryzias latipes) with or without a neighbouring conspecific. It was found that individual medaka male fish preferred a light environment and avoided a dark environment, whereas the display of a neighbouring conspecific enhanced the time the male spent in the dark environment (i.e., this condition encouraged risk-taking). The blood glucose level increased in fish confined to the dark condition but did not increase in light-preferring fish and risk-taking fish. Large somata expressing tyrosine hydroxylase, which is the rate-limiting enzyme in dopamine synthesis, were detected in the telencephalic and diencephalic brain regions in risk-taking medaka, whereas large somata were detected in the diencephalic region in medaka confined to the dark condition. These findings indicated that medaka is a good fish model to explore the central roles of dopaminergic neurons in the telencephalon and the diencephalon, which regulate risk-taking behaviour. © 2020 The Fisheries Society of the British Isles.Progress is needed before explicit photodynamic therapy (PDT) dosimetry can treat peritoneal carcinomatosis and yet spare all healthy tissue. A report by Cengel et al. in this issue of Photochemistry & Photobiology on tissue evaluation in a canine model may bring that goal a step closer and may even be dogma-changing. © 2020 American Society for Photobiology.Larval dispersion rather than adult migration generally leads to the worldwide expansion of fishes. Species of the genus Gymnocanthus have expanded geographically while undergoing allopatric speciation. Of this genus, while Gymnocanthus tricuspis inhabits the Arctic Ocean and surrounding area, G. herzensteini and G. Selleck Captisol intermedius occur around northern Japan. Larval early life histories of G. herzensteini and G. intermedius from northern Japan and G. tricuspis from Unalaska Island were investigated to estimate their dispersal potential during larval stages. The larval and juvenile abundances of G. herzensteini and G. intermedius were highest in May in shallow sandy bottoms below 7 m in depth, and the body sizes were 9.7-34.6 mm notochord length (NL) and/or standard length (SL) in G. herzensteini and 8.4-46.7 mm NL and/or SL in G. intermedius. Two egg masses of G. tricuspis (1.92 ± 0.08 mm in diameter) and hatched larvae (6.20 ± 0.19 mm NL) were collected in March. Compared with other sculpins in previous studies, the body sizes of G. herzensteini and G. intermedius at hatch are large and at settlement are small, while both hatch and settlement sizes of G. tricuspis are much larger. Counting micro-increments between the hatch check and settlement marks in G. herzensteini and G. intermedius demonstrated that the pelagic larval durations for 2 weeks with an immature body suggests that these species cannot disperse widely during the pelagic phase, while pelagic larvae of Arctic species such as G. tricuspis with long pelagic larval durations could disperse. © 2020 The Fisheries Society of the British Isles.One specimen of the boreal Clupea harengus (Clupeidae) was caught southerly, in the Gulf of Cádiz (southern Spain), whereas a specimen of the subtropical Epinephelus aeneus (Serranidae) was caught northerly, in Galician waters (north-west of Spain). These catches represent a new southernmost record in the eastern Atlantic for C. harengus and the second northernmost for E. aeneus. The co-occurrence of warm and cold affinity fishes in temperate latitudes is unusual, but the existence of anomalies in the temperature of the Atlantic waters could be behind these findings. © 2020 The Fisheries Society of the British Isles.Passive integrated transponder (PIT)-tagging is commonly used in behavioural studies of fish, although long-term evaluations of effects from tagging under natural conditions are scarce. We PIT-tagged common bream Abramis brama, European perch Perca fluviatilis, pike Esox lucius and roach Rutilus rutilus, released them in their lakes of origin and recaptured them after 103-3269 days. Overall, tagged fish did not differ in condition from non-tagged fish, except for small R. rutilus that had a lower length-specific body mass in one lake in 1 year. We conclude that PIT-tagging in general has negligible long-term effects on fish condition. © 2020 The Fisheries Society of the British Isles.The Mekong Delta is host to a large number of freshwater species, including a unique group of facultative air-breathing Anabantiforms. Of these, the striped snakehead (Channa striata), the climbing perch (Anabas testudineus), the giant gourami (Osphronemus goramy) and the snakeskin gourami (Trichogaster pectoralis) are major contributors to aquaculture production in Vietnam. The gastrointestinal responses to feeding in these four species are detailed here. Relative intestinal length was lowest in the snakehead, indicating carnivory, and 5.5-fold greater in the snakeskin, indicating herbivory; climbing perch and giant gourami were intermediate, indicating omnivory. N-waste excretion (ammonia-N + urea-N) was greatest in the carnivorous snakehead and least in the herbivorous snakeskin, whereas the opposite trend was observed for net K+ excretion. Similarly, the more carnivorous species had a greater stomach acidity than the more herbivorous species. Measurements of acid-base flux to water indicated that the greatest postprandial alkaline tide occurred in the snakehead and a potential acidic tide in the snakeskin. Additional findings of interest were high levels of both PCO2 (up to 40 mmHg) and HCO3 - (up to 33 mM) in the intestinal chyme of all four of these air-breathing species. Using in vitro gut sac preparations of the climbing perch, it was shown that the intestinal net absorption of fluid, Na+ and HCO3 - was upregulated by feeding but not net Cl- uptake, glucose uptake or K+ secretion. Upregulated net absorption of HCO3 - suggests that the high chyme (HCO3 - ) does not result from secretion by the intestinal epithelium. The possibility of ventilatory control of PCO2 to regulate postprandial acid-base balance in these air-breathing fish is discussed. © 2020 The Fisheries Society of the British Isles.