Crystal structure, Hirshfeld surface, and DFT studies of 4-((pyrrolidin-1-ylsulfonyl)methyl)aniline

The crystal structure investigation of the title compound 4-((pyrrolidin-1-ylsulfonyl) methyl)aniline (PSMA) C11H16N2O2S shows that the molecule is essentially coplanar with a dihedral angle of 26.70(14)°between the pyrrolidine and the benzene rings. A pair of strong N-H···O hydrogen bonds produces continuous two-dimensional sheets with R22(18) ring motifs. The crystal structure also features a weak C-H···π interaction resulting in a three-dimensional network. Density functional theory (DFT) calculations reveal that the experimental and calculated geometric parameters of the molecule are nearly the same. Hirshfeld surface analysis has been carried out to study the various intermolecular interactions responsible for the crystal packing. Theoretical calculations indicate an excellent correlation between the experimental and the simulated UV spectra.

B-Mode Ultrasound, a Reliable Tool for Monitoring Experimental Intracerebral Hemorrhage

Background: Magnetic resonance imaging (MRI) is currently used for the study of intracerebral hemorrhage (ICH) in animal models. However, ultrasound is an inexpensive, non-invasive and rapid technique that could facilitate the diagnosis and follow-up of ICH. This study aimed to evaluate the feasibility and reliability of B-mode ultrasound as an alternative tool for in vivo monitoring of ICH volume and brain structure displacement in an animal model.Methods: A total of 31 male and female Sprague-Dawley rats were subjected to an ICH model using collagenase-IV in the striatum following stereotaxic references. The animals were randomly allocated into 3 groups: healthy (n = 10), sham (n = 10) and ICH (n = 11). B-mode ultrasound studies with a 13-MHz probe were performed pre-ICH and at 5 h, 48 h, 4 d and 1 mo post-ICH for the assessment of ICH volume and displacement of brain structures, considering the distance between the subarachnoid cisterns and the dura mater. The same variables were studied by MRI at 48 h and 1 mo post-ICH.Results: Both imaging techniques showed excellent correlation in measuring ICH volume at 48 h (r = 0.905) and good at 1 mo (r = 0.656). An excellent correlation was also observed in the measured distance between the subarachnoid cisterns and the dura mater at 1 mo between B-mode ultrasound and MRI, on both the ipsilateral (r = 0.870) and contralateral (r = 0.906) sides of the lesion.Conclusion: B-mode ultrasound imaging appears to be a reliable tool for in vivo assessment of ICH volume and displacement of brain structures in animal models.

The Monthly Variation Tendency of Microcystin-LR Levels in The Huangpu River (China) by Applications of ELISA and HPLC

In this study, the contents of microcystin-LR (MC-LR) of Microcystis aeruginosa cultures in the laboratory and natural water samples from the Huangpu River in different seasons were detected through enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. Excellent correlation between the two methods was obtained (R2 > 0.99). ELISA was a reliable and simple method with high reproducibility (coefficient of variation < 25%) and satisfactory recovery for the monitoring of low levels of MC-LR. MC-LR concentrations in Huangpu River varied with the seasonal variation,which peaked in August with the temperature over 30°C and then gradually declined with the decreasing temperature after August. The highest MC-LR concentration in the Huangpu River was below the WHO drinking water quality standard (1 ug/L). These results indicated that warm temperature accelerated the MC-LR synthesis and release, and it is necessary to regularly monitor the MC-LR levels, especially during the high algae period in summer. ELISA can be applied to detect the low levels of MC-LR in the field without complex treatment, avoiding the samples from denaturation and degradation during the transportation. Hence, ELISA is a better alternative of HPLC when HPLC is unavailable, especially when rapid testing is required in routine MC-LR analysis.

Accuracy of the Apple Watch single-lead ECG recordings in pre-term neonates

Introduction: Telemedicine gained an increasing use throughout the last years. Lifestyle tools like the Apple watch seem to have an increasing spread even in remote areas and underdeveloped regions. The increasing availability of these tools offers the chance to use the health care functions of these devices to improve provision of professional medical care. First data on the use of the Apple Watch as a remote monitoring device in children have been reported, showing good acceptability and usability of the Apple Watch for symptom monitoring in children. This study aimed to evaluate the accuracy of the Apple Watch iECG in comparison to a standard 12-lead ECG in pre-term babies. Methods: In this prospective, single-arm study, consecutive preterm neonates hospitalised in Leipzig University Hospital neonatal ICU were eligible. A 12-lead ECG and an iECG using Apple Watch 4 were performed. iECG and 12-lead ECG measurements were performed by a paediatric cardiologist. Cardiac rhythm was classified and amplitudes and timing intervals were analysed for comparability. Results: Fifty preterm neonates, gestational week (23–36 weeks), and body weight (0.65–3.09 kg) were enrolled. Overall good quality and excellent correlation of the Apple Watch generated iECG in comparison to the standard 12-lead ECG could be demonstrated (p < 0.001). When interpreted by a paediatric cardiologist, a correct rhythm classification could be done in 100% of cases. Conclusion: The Apple Watch iECG seems to be a valuable tool to record an ECG comparable to lead I of the standard 12-lead ECG even in pre-term neonates. With a widespread availability and excellent connectivity, the Apple Watch iECG function may provide practitioners with a tool to send an iECG for interpretation to a paediatric cardiac specialist.

On the tribology of complex 2D/3D composites bearing

In the present work, a hierarchical braided polymer composite consists of Polytetrafluoroethylene (PTFE) fibers, reinforcement fibers, and epoxy resin was designed as a self-lubricant composite and bearing. Different reinforcements such as glass, carbon, and Kevlar fibers were employed to investigate the effect of reinforcement on the wear characteristics of composites. Besides, the influence of 2D/3D braid fabric was examined on the wear behavior of samples. Also, 90 and 120 N loads were applied to assess the load impact. Results illustrated that compared to glass and Kevlar, carbon could lead to a greater wear weight loss and friction coefficient. However, PTFE tribofilm was observed according to scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDS) analysis. Moreover, with the increase of load, the wear stability of the composites faded significantly. Furthermore, the tribological features became inappropriate with the deployment of the 3D braid structure. Finally, the modeling of tribological parameters was carried out using response surface methodology-based D-optimal design. The adequacy of the models was checked by analysis of variance. Results implied that there is an excellent correlation between the model and the experiments.

Use of Bivalirudin-Specific Monitoring Assays in Ventricular Assist Device Patients

Increasing numbers of pediatric ventricular assist device (VAD) patients are being anticoagulated with the parenteral direct thrombin inhibitor bivalirudin because it is reportedly associated with fewer bleeding and thrombotic events. With expanded use, management is shifting from a handful of experts to a wider pool of clinicians and trainees, increasing the importance of identifying broadly acceptable, standardized monitoring assays. The pharmacokinetics of bivalirudin have not been well-studied in the pediatric population and drug monitoring in all ages has been problematic for critically ill patients who require intermediate or longer-term therapeutic anticoagulation. The dilute thrombin time (dTT), available in many clinical laboratories, has been suggested as a potentially superior alternative to the activated partial thromboplastin time (aPTT), but results have been inconsistent. As clinical use of the dTT (c-dTT) for monitoring bivalirudin increased at our institution, we sought to evaluate the performance of commercially available, "research only" functional bivalirudin assays with calibrators and controls to measure bivalirudin's anticoagulation effect, utilizing residual plasmas and clinical data from VAD patients treated with bivalirudin. Residual citrated, platelet poor plasma samples from clinically ordered laboratory tests in VAD patients were collected and stored frozen at -70 oC from February 8, 2018, to January 4, 2021. With IRB approval, the samples were analyzed in conjunction with medical record review. Two experimental assay kits were utilized, ex-dTT: a dilute thrombin time assay (Hemoclot, Hyphen-Biomed, FR) and ex-anti FIIa: a chromogenic anti-factor IIa assay (BiophenDTI, Hyphen-Biomed, FR). Bivalirudin calibrators (Biophen, Hyphen-Biomed, FR) were used to develop a standard curve for the assays. Controls of low and high (1.5 and 4 microgram/mL) bivalirudin (Biophen, Hyphen-Biomed, FR) were used for quality control of the assays. Results from the two experimental assays were compared with available standard laboratory monitoring when results were available. In total, 115 residual plasma samples from 11 different patients (up to 16 samples per patient) were analyzed. Subjects included 1 adult (37 yr.) and 10 pediatric patients (0-18 yr.). There was excellent correlation between the two experimental assays (Fig. 1A). Correlation was good between the c-dTT and each of the experimental assays; however, with a clinical laboratory platform change (instrument, reagents) midway through sample collection, the c-dTT results shifted substantially in their corresponding estimate of bivalirudin concentration (Figs 1B and C). Activated partial thromboplastin time (aPTT) had poor correlation with the c-dTT and with each of the experimental assays (Fig. 1D). Here we report results from two commercially available kits that estimate bivalirudin concentration using dTT or chromogenic anti-factor IIa assays, in comparison with clinically generated results from VAD patients treated with bivalirudin. Our findings agree with previous observations that the aPTT shows poor correlation with dTT assays (clinically used and experimental) over days and weeks of anticoagulation. The two experimental assays had excellent correlation with each other and good correlation with the c-dTT; however, the fact that the c-dTT results shifted dramatically with a clinical laboratory platform change is illustrative of the need for a bivalirudin-specific monitoring assay as an essential tool for improving outcomes at our center and across centers. More research is needed to understand which type of monitoring assay (dTT or anti-FIIa) may be better suited to particular clinical circumstances. Figure 1 Figure 1. Disclosures Lorts: Abbott: Consultancy; Medtronic: Consultancy; Berlin Heart: Consultancy; Syncardia: Consultancy; Abiomed: Consultancy.

Photodynamic Therapy Targeting Macrophages Using IRDye700DX-Liposomes Decreases Experimental Arthritis Development

Macrophages play a crucial role in the initiation and progression of rheumatoid arthritis (RA). Liposomes can be used to deliver therapeutics to macrophages by exploiting their phagocytic ability. However, since macrophages serve as the immune system’s first responders, it is inadvisable to systemically deplete these cells. By loading the liposomes with the photosensitizer IRDye700DX, we have developed and tested a novel way to perform photodynamic therapy (PDT) on macrophages in inflamed joints. PEGylated liposomes were created using the film method and post-inserted with micelles containing IRDye700DX. For radiolabeling, a chelator was also incorporated. RAW 264.7 cells were incubated with liposomes with or without IRDye700DX and exposed to 689 nm light. Viability was determined using CellTiterGlo. Subsequently, biodistribution and PDT studies were performed on mice with collagen-induced arthritis (CIA). PDT using IRDye700DX-loaded liposomes efficiently induced cell death in vitro, whilst no cell death was observed using the control liposomes. Biodistribution of the two compounds in CIA mice was comparable with excellent correlation of the uptake with macroscopic and microscopic arthritis scores. Treatment with 700DX-loaded liposomes significantly delayed arthritis development. Here we have shown the proof-of-principle of performing PDT in arthritic joints using IRDye700DX-loaded liposomes, allowing locoregional treatment of arthritis.

Synthesis, Single Crystal X-ray, Hirshfeld and DFT Studies of 1,8-Dichloro-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic Acid

In this paper, synthesis, single-crystal X-ray structure, Hirshfeld and DFT studies of 1,8-dichloro-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic acid are discussed. Different intermolecular contacts affecting the crystal stability are studied using Hirshfeld calculations. The H…Cl and O…H contacts are the most significant, showing corresponding interaction distances of 2.731 Å (Cl2…H10) and 1.681Å (H1…O1), 2.328 Å (O1…H13), 2.510 Å (O1…H12) based on Hirshfeld calculations. DFT calculations are carried out to study the electronic behavior, as well as the 1H- and 13C-NMR spectra of the synthesized compound. The computed NMR chemical shifts show excellent correlation with the experimental data (R2 = 0.9884–0.9705).

Comparison among TonoVet, TonoVet Plus, Tono-Pen Avia Vet, and Kowa HA-2 portable tonometers for measuring intraocular pressure in dogs

Background and Aim: Tonometers are an important instrument for measuring intraocular pressure (IOP) in the diagnosis of glaucoma or uveitis. This study aimed to compare the accuracy of the main types of tonometers with different IOP measurement methodologies in dogs: TonoVet and TonoVet Plus (rebound), Tono-Pen Avia Vet (applanation), and Kowa HA-2 (Goldmann applanation). Materials and Methods: IOP was measured in 152 eyes of 76 dogs. A postmortem study was performed by comparing manometry and tonometry values and calculating the correlation coefficient (r2), in vivo real IOP (manometry) among the tonometers was compared, and an outpatient study was conducted with healthy eyes and eyes with signs of glaucoma and uveitis. Results: In the postmortem study, the values of r2 in descending order were Kowa (0.989), TonoVet Plus (0.984), TonoVet (0.981), and Tono-Pen Avia Vet (0.847). The IOP values in mmHg in the in vivo study were as follows: Aneroid manometer (16.8±2.5.7), TonoVet (18.1±2.9), TonoVet Plus (20.6±2.3), Tono-Pen Avia Vet (17.1±2.5), and Kowa (16.1±1.7); in outpatient clinics: TonoVet (16.8±3.8), TonoVet Plus (19.2±2.9), Tono-Pen Avia Vet (16.2±2.4), and Kowa (15.0±1.3); glaucoma: TonoVet (30.2±3.5), TonoVet Plus (35.0±6.1), Tono-Pen Avia Vet (29.5±4.2), and Kowa (23.9±5.0); and uveitis: TonoVet (14.2±1.4), TonoVet Plus (17.6±1.9), Tono-Pen Avia Vet (13.7±2.1), and Kowa (12.6±1.7). Conclusion: There was a strong correlation between IOP values and manometry in all the tonometers. The highest values were obtained with TonoVet Plus and the lowest with Kowa HA-2. All tonometers accurately measured IOP in dogs, including the latest TonoVet Plus, which showed an excellent correlation coefficient.

Quantitative myocardial perfusion SPECT/CT for the assessment of myocardial tracer uptake in patients with three-vessel coronary artery disease: Initial experiences and results

Background To evaluate quantitative myocardial perfusion SPECT/CT datasets for routine clinical reporting and the assessment of myocardial tracer uptake in patients with severe TVCAD. Methods MPS scans were reconstructed as quantitative SPECT datasets using CTs from internal (SPECT/CT, Q_INT) and external (PET/CT, Q_EXT) sources for attenuation correction. TPD was calculated and compared to the TPD from non-quantitative SPECT datasets of the same patients. SUVmax, SUVpeak, and SUVmean were compared between Q_INT and Q_EXT SPECT datasets. Global SUVmax and SUVpeak were compared between patients with and without TVCAD. Results Quantitative reconstruction was feasible. TPD showed an excellent correlation between quantitative and non-quantitative SPECT datasets. SUVmax, SUVpeak, and SUVmean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUVmean differed significantly between the two groups. Global SUVmax and SUVpeak were significantly reduced in patients with TVCAD. Conclusions Absolute quantification of myocardial tracer uptake is feasible. The method seems to be robust and principally suitable for routine clinical reporting. Quantitative SPECT might become a valuable tool for the assessment of severe coronary artery disease in a setting of balanced ischemia, where potentially life-threatening conditions might otherwise go undetected.