Impact Of The Placement And Quality Of Face-To-Face Meetings In A Hybrid Distance Learning Course

As online and hybrid courses are becoming a wide-spread option for higher education, researchers are exploring various delivery methods.  Hybrid courses involve blending two modes of interaction –both face-to-face as well as online.  The exact distribution and timing of face-to-face meetings verse online delivery is a question that instructors have been struggling with since the inception of hybrid courses.  This paper reports findings from a study evaluating course outcomes in an undergraduate business computer applications course based on the quality and quantity of face to face meetings at the beginning of the course.&nbsp

Conformational Studies of Carnitine and Acetylcarnitine: Design and Synthesis of Active-Site Probes of Carnitine Acetyltransferase.

The conformations of carnitine (Cn) and acetylcarnitine (AcCn) have been investigated through a combination of methods. The solid-state structures of their zwitter-ionic forms have been determined by single-crystal X-ray analyses. The crystal structures reveal different backbone conformations for the two molecules. Carnitine exists in an extended conformation (a,g \sp- conformations for the C1-C2-C3-C4 and N1-C4-C3-O3 torsion angles, respectively), while AcCn exhibits a folded conformation (g\sp-,g\sp-). The solution conformations of Cn and AcCn have been investigated by high resolution \sp1H NMR coupling data. A simple equation has been developed for the prediction of torsion angles from \sp3 J (HCCH) coupling constants. This equation employs experimentally determined substituent constants, which can account for solvent effects. The conformation and populations of conformers of AcCn and Cn in D\sb2O have been estimated by use of this new Karplus relationship. The assignment of diasteriotopic protons of Cn and AcCn was made by analogy with the lowest energy conformations as determined by molecular mechanics (MM2) calculations parameterized with atomic charges from ab initio (3-21G) calculations. Populations of conformers, arising from rotation about the C2-C3 and C3-C4 bonds were calculated. Both compounds adopt a highly preferred g\sp- conformation about the N1-C4-C3-O3 torsion angle. In contrast, the C1-C2-C3-C4 torsion angle exhibits substantial rotational freedom between g\sp- and a. In Cn the anti conformer dominates, whereas in AcCn the g\sp- conformer is most prevalent. The relative energetics of extended and folded conformers suggest that binding of either Cn or AcCn to carnitine acetyltransferase (CAT) occurs with the folded form. The syntheses of seventeen conformationally rigid morpholinium analogues of Cn and AcCn are described. These compounds exhibit predictable stereo- and regio-chemistry because of stereospecific ring closures of their acyclic precursors. The single-crystal X-ray structures for seven of the compounds are presented. The synthesis, resolution, and solid-state structure of a sulfonate analogue of Cn (sulfocarnitine) are also described. These compounds have been tested as inhibitors of pigeon CAT and rat-liver carnitine palmitoyltransferase (CPT). The results support the hypothesis of a folded conformation for enzyme-bound Cn or AcCn. The inhibitors also reveal distinctly different modes of Cn recognition by CAT compared to CPT

Attenuation of coronary vascular resistance by selective alpha1,-adrenergic blockade in patients with coronary artery disease

Alpha-adrenergic-mediated coronary vasoconstriction during stress such as cold pressor testing may contribute to myocardial ischemia by increasing coronary vascular resistance in patients with severe coronary artery disease. Nonselective alpha-receptor blockade with phen-tolamine abolishes both the peripheral and coronary vasoconstriction during cold pressor testing, but causes reflex tachycardia and increased inotropy. To determine the role of selective alpha1-receptor blockade, the changes in coronary vascular resistance during cold pressor testing were measured in 18 patients with coronary artery disease before and after intravenous administration of 100 mg of trimazosin. Cold pressor testing was performed at a constant paced subanginal heart rate of 95 ± 5 beats/min (± 1SD). Before trimazosin, cold pressor testing increased mean arterial pressure by 9 ± 4% (102 ± 14 to 111 ± 14 mm Hg, p < 0.001) with no change in coronary sinus blood flow, but significantly increased coronary vascular resistance by 15 ± 19% (1.02 ± 0.46 to 1.15 ± 0.57 units, p < 0.05). Five minutes after trimazosin, cold pressor testing increased mean arterial pressure by 6 ± 5% (p < 0.001) with a marked attenuation of the increase in coronary vascular resistance (6 ± 11%, p = NS), which was significantly less than before trimazosin (p < 0.02). Trimazosin did not increase plasma norepinephrine concentration at rest, suggesting that in the dosage used trimazosin caused selective alpha1-receptor blockade.These data suggest that although the hypertensive response to cold pressor testing is somewhat blunted by selective alpha1,-adrenoceptor blockade, the reflex coronary vasoconstriction during adrenergic stimulation in some patients with coronary artery disease can be significantly attenuated. Use of agents that block alpha2-adrenoceptors has been clinically unsatisfactory because of the adverse myocardial effects of increased norepinephrine release. Selective alpha1-receptor blockade may have an additional advantage over nonselective alpha-adrenergic blockade in that the release of norepinephrine is also attenuated, thus potentially producing less augmentation of heart rate and myocardial oxygen demand

Nuggets, Pearls, and Vignettes of Master Heart Failure Clinicians

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73696/1/j.1527-5299.2001.00307.x.pd

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Ototoxin-induced cellular damage in neuromasts disrupts lateral line function in larval zebrafish

The ototoxicity of a number of marketed drugs is well documented, and there is an absence of convenient techniques to identify and eliminate this unwanted effect at a pre-clinical stage. We have assessed the validity of the larval zebrafish, or more specifically its lateral line neuromast hair cells, as a microplate-scale in vivo surrogate model of mammalian inner ear hair cell responses to ototoxin exposure. Here we describe an investigation of the pathological and functional consequences of hair cell loss in lateral line neuromasts of larval zebrafish after exposure to a range of well known human and non-human mammalian ototoxins. Using a previously described histological assay, we show that hair cell damage occurs in a concentration-dependent fashion following exposure to representatives from a range of drug classes, including the aminoglycoside antibiotics, salicylates and platinum-based chemotherapeutics, as well as a heavy metal. Furthermore, we detail the optimisation of a semi-automated method to analyse the stereotypical startle response in larval zebrafish, and use this to assess the impact of hair cell damage on hearing function in these animals. Functional assessment revealed robust and significant attenuation of the innate startle, rheotactic and avoidance responses of 5 day old zebrafish larvae after treatment with a number of compounds previously shown to induce hair cell damage and loss. Interestingly, a startle reflex (albeit reduced) was still present even after the apparent complete loss of lateral line hair cell fluorescence, suggesting some involvement of the inner ear as well as the lateral line neuromast hair cells in this reflex response. Collectively, these data provide evidence to support the use of the zebrafish as a pre-clinical indicator of drug-induced histological and functional ototoxicity

Syntheses, Structures, and Enzymatic Evaluations of Hemiacylcarnitiniums, a New Class of Carnitine Acyltransferase Inhibitors

The syntheses of (2S,6R)-6-(carboxymethyl)-2-hydroxy-2,4,4-trimethylmorpholinium chloride (hemiacetylcamitinium, HAC), (2S,6R)-6-(carboxymethyl)-2-ethyl-2-hydroxy-4,4-dimethylmorpholinium bromide (hemipropanoylcarnitinium, HPrC), and (2S,6R)-6-(carboxymethyl)-2-hydroxy-4,4-dimethyl-2-phenylmorpholinium chloride monohydrate (hemibenzoylcarnitinium, HBC) are described. The crystal structure of HAC is reported and compared with crystal structures of HPrC, HBC, carnitine·HCl, acetylcarnitine·HCl, and acetylcamitine·HCl·H2O. HAC, HPrC, and HBC inhibit carnitine acetyltransferase (CAT) activity from multiple biological sources. The best inhibitor, HAC, has Ki of 69 ± 5 μM with rat liver peroxisomal CAT. HAC binds more strongly than the natural substrate (and isomer), acetylcarnitine. HAC also strongly inhibits, Ki = 92 ± 14 μM, CAT from rat heart mitochondria. HPrC inhibits pigeon breast CAT with a Ki, of 200 ± 30 μM. HBC inhibits pigeon breast CAT, rat heart mitochondrial CAT, rat liver mitochondrial CAT, and rat liver peroxisomal carnitine octanoyltransferase (COT), with values of Ki of 3500 ± 500,2400 ± 70,1670 ± 70, and 1100 ± 100 μM, respectively. Racemic 6-(carboxymethyl)-2-hydroxy-2-pentadecyl-4,4-dimethylmorpholinium bromide (hemipalmitoylcamitinium, HPC) strongly inhibits (Ki = 2 ± 0.3 μM) beef liver mitochondrial CPTi. In summary, hemiacylcarnitiniums show promise as a general class of carnitine acyltransferase inhibitors.</p