Optimization of production yields, radionuclidic purity and hotcell shielding of SPECT and PET radionuclides produced by proton irradiation in variable energy 30 MeV cyclotrons--Part 67Ga.

Optimization of the production parameters (incident and exit proton energy, thickness of the (68)Zn target layer, decay time to start chemical processing of an irradiated target after the end of bombardment) and of the thickness of the lead shield of the processing hotcell for the cyclotron production of (67)Ga by the (68)Zn(p,2n) threshold reaction are accomplished by powerful divide et impera and binary search algorithms with the Pharmacopoeia radionuclidic purity of the (67)Ga-citrate radiopharmaceutical at a reference time and the locally accepted dose rate level for the controlled area as boundary conditions. Two sets of equations are presented (one associated with the maximum production rate, the other with the use of a minimum target layer thickness) that allow the expression of the optimized production parameters, the radionuclide yields satisfying the Pharmacopoeia requirements at the start of distribution and the necessary shielding as a function of the required activity at the start of distribution and of the maximum allowable beam current on target.     

Delayed Extension Block Pinning in 27 Patients With Mallet Fracture

Background: Untreated bony mallet fingers can cause an array of problems; therefore, adequate treatment is essential. The primary aim of this study was to determine the patient-reported functional outcome of delayed surgical intervention of bony mallet fingers. The secondary aim was to determine the complication rate of delayed surgical intervention. Methods: In this single-center retrospective cohort study, all consecutive patients treated between 2010 and 2016 at our level 2 regional teaching hospital were included. Inclusion criterion was a bony mallet finger injury (excluding the thumb), presenting >21 days after injury, treated with extension block pinning. Indications for surgery were >2 mm fragment displacement or volar subluxation of the distal interphalangeal joint. Six to 82 months postoperatively, patients completed the Patient-Rated Wrist and Hand Evaluation (PRWHE) by phone. Complications were extracted by chart review. Results: Twenty-seven patients were included, and all completed the PRWHE. Median time to surgery was 35 days (interquartile range [IQR] = 29-42; range = 22-61). Reasons for delay in surgical treatment were patient/physician delay in 24 cases and failed conservative treatment in 3 cases. The median PRWHE score was 0 (IQR = 0-5; range = 0-22.5). After retrospective assessment of the outpatient charts, no early symptoms of malunion or nonunion were found. One patient had a loss of Kirschner-wire fixation, which was corrected. Three patients had an infection that required antibiotic treatment. Conclusions: Delayed surgical management of bony mallet fingers demonstrated adequate functional outcome with minimal complications when compared with prior literature.     

3-Nitropropionic acid induces a spectrum of Huntington's disease-like neuropathology in rat striatum

Systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) to rats results in selective striatal lesions and serves as an experimental model of Huntington's disease (HD). However, the effects of the 3-NP treatment are unpredictable and result in lesions of variable severity. The present study was aimed at further characterizing the variability of the striatal lesions induced by systemic administration of 3-NP using osmotic pumps. Hematoxylin-eosin (HE) and Nissl stains as well as immunohistochemical labelling of astrocytes and striatal neurones were performed to analyse the neurotoxic effects of 3-NP. In general, chronic systemic administration of 3-NP resulted in obvious bilateral striatal lesions, which ranged from mild to severe, together with a subtle, but detectable behavioural lesion. Severe type lesions showed marked neuronal loss and an increased expression of glial fibrillary acidic protein (GFAP) in astrocytes surrounding the lesion area, whereas in the core of the lesion GFAP-immunoreactivity was absent. The mild type lesion was characterized by a substantial loss of striatal neurones and an increased expression of GFAP-positive astrocytes throughout the lesion. In a number of 3-NP-treated animals, neither type of lesion was observed, although these animals demonstrated behavioural changes in the paw test compared to controls. In the striatum of these tested 3-NP-treated animals, compromised rk' neurones were detected, suggestive of subtle and early 3-NP-induced neuronal injury. Similar dark neurones were also detected in mild and severe lesions and were immunocytochemically characterized as gamma-aminobutyric acid (GABA) and substance P containing spiny neurones, which belong to the neuronal population that is affected in early HD. These results indicate that systemic administration of 3-NP to rats may result in a spectrum of striatal pathology of which the morphology of the mild type lesion resembles the characteristic HD neuropathology most closely.     

Reliability and Validity of Assessing User Satisfaction With Web-Based Health Interventions

BackgroundThe perspective of users should be taken into account in the evaluation of Web-based health interventions. Assessing the users’ satisfaction with the intervention they receive could enhance the evidence for the intervention effects. Thus, there is a need for valid and reliable measures to assess satisfaction with Web-based health interventions.ObjectiveThe objective of this study was to analyze the reliability, factorial structure, and construct validity of the Client Satisfaction Questionnaire adapted to Internet-based interventions (CSQ-I).MethodsThe psychometric quality of the CSQ-I was analyzed in user samples from 2 separate randomized controlled trials evaluating Web-based health interventions, one from a depression prevention intervention (sample 1, N=174) and the other from a stress management intervention (sample 2, N=111). At first, the underlying measurement model of the CSQ-I was analyzed to determine the internal consistency. The factorial structure of the scale and the measurement invariance across groups were tested by multigroup confirmatory factor analyses. Additionally, the construct validity of the scale was examined by comparing satisfaction scores with the primary clinical outcome.ResultsMultigroup confirmatory analyses on the scale yielded a one-factorial structure with a good fit (root-mean-square error of approximation =.09, comparative fit index =.96, standardized root-mean-square residual =.05) that showed partial strong invariance across the 2 samples. The scale showed very good reliability, indicated by McDonald omegas of .95 in sample 1 and .93 in sample 2. Significant correlations with change in depressive symptoms (r=−.35, P<.001) and perceived stress (r=−.48, P<.001) demonstrated the construct validity of the scale.ConclusionsThe proven internal consistency, factorial structure, and construct validity of the CSQ-I indicate a good overall psychometric quality of the measure to assess the user’s general satisfaction with Web-based interventions for depression and stress management. Multigroup analyses indicate its robustness across different samples. Thus, the CSQ-I seems to be a suitable measure to consider the user’s perspective in the overall evaluation of Web-based health interventions.     

Influence of Orientation and Radiative Heat Transfer on Aluminum Foams in Buoyancy-Induced Convection

Two differently-produced open-cell aluminum foams were compared to a commercially available finned heat sink. Further, an aluminum plate and block were tested as a reference. All heat sinks have the same base plate dimensions of four by six inches. The first foam was made by investment casting of a polyurethane preform and has a porosity of 0.946 and a pore density of 10 pores per linear inch. The second foam is manufactured by casting over a solvable core and has a porosity of 0.85 and a pore density of 2.5 pores per linear inch. The effects of orientation and radiative heat transfer are experimentally investigated. The heat sinks are tested in a vertical and horizontal orientation. The effect of radiative heat transfer is investigated by comparing a painted/anodized heat sink with an untreated one. The heat flux through the heat sink for a certain temperature difference between the environment and the heat sink’s base plate is used as the performance indicator. For temperature differences larger than 30 ^°C, the finned heat sink outperforms the in-house-made aluminum foam heat sink on average by 17%. Furthermore, the in-house-made aluminum foam dissipates on average 12% less heat than the other aluminum foam for a temperature difference larger than 40 ^°C. By painting/anodizing the heat sinks, the heat transfer rate increased on average by 10% to 50%. Finally, the thermal performance of the horizontal in-house-made aluminum foam heat sink is up to 18% larger than the one of the vertical aluminum foam heat sink.     

A randomized cross-over trial to define neurophysiological correlates of AV-101 N-methyl-d-aspartate receptor blockade in healthy veterans

The kynurenine pathway (KP) is a strategic metabolic system that combines regulation of neuronal excitability via glutamate receptor function and neuroinflammation via other KP metabolites. This pathway has great promise in treatment of depression and suicidality. The KP modulator AV-101 (4-chlorokynurenine, 4-Cl-KYN), an oral prodrug of 7-chlorokynurenic acid (7-Cl-KYNA), an N-methyl-d-aspartate receptor (NMDAR) glycine site antagonist, and of 4-chloro-3-hydroxyanthranilic acid (4-Cl-3-HAA), a suppressor of NMDAR agonist quinolinic acid (QUIN), is a promising potential antidepressant that targets glutamate functioning via the KP. However, a recent placebo-controlled clinical trial of AV-101 in depression found negative results. This raises the question of whether AV-101 can penetrate the brain and engage the NMDAR and KP effectively. To address this problem, ten healthy US military veterans (mean age = 32.6 years ± 6.11; 1 female) completed a phase-1 randomized, double-blind, placebo-controlled, crossover study to examine dose-related effects of AV-101 (720 and 1440 mg) on NMDAR engagement measured by γ-frequency band auditory steady-state response (40 Hz ASSR) and resting EEG. Linear mixed models revealed that 1440 mg AV-101, but not 720 mg, increased 40 Hz ASSR and 40 Hz ASSR γ-inter-trial phase coherence relative to placebo. AV-101 also increased 4-Cl-KYN, 7-Cl-KYNA, 4-Cl-3-HAA, 3-HAA, and KYNA in a dose-dependent manner, without affecting KYN and QUIN. AV-101 was safe and well tolerated. These results corroborate brain target engagement of 1440 mg AV-101 in humans, consistent with blockade of interneuronal NMDAR blockade. Future studies should test higher doses of AV-101 in depression. Suicidal behavior, which has been associated with high QUIN and low KYNA, is also a potential target for AV-101.Subject terms: Biomarkers, Neurophysiology, Neuroscience     

Prior use of anticoagulation is associated with a better survival in COVID-19

Journal of Thrombosis and Thrombolysis - Coronavirus disease 2019 (COVID-19) is associated with a high incidence of venous and arterial thromboembolic events. The role of anticoagulation (AC) prior...