The M.K.M. suppression test: Its use as a prescription criteria

The M.K.M. suppression test: Its use as a prescription criteri

Post-Implementation Evidence-Based Decision Making: The Telehealth Assessment Tool For Health (TeATH)

Few telehealth implementations survive the initial pilot phase, and any anticipated Return on Investment seldom materialises. Within South Africa a reason is the lack of post-implementation monitoring and assessment. To address this practice gap we developed a simple and practical tool to allow decision- and policy-makers to assess the post-implementation state of current telehealth applications. Recognised management approaches were reviewed, and elements adopted or adapted to develop the new decision support tool. A systems-based approach, applying a revised People, Process, and Technology methodology (incorporating Infrastructure), and Balanced Score Card and e-Readiness principles, was applied. This allowed development of the Telehealth Assessment Tool for Health (TeATH), whose utility was demonstrated by assessing the current performance of existing teleradiology implementations in three Provincial hospitals in Mpumalanga Province. Expected results were achieved, with TeATH revealing fair performance in the Technology dimension, but poor performance across People, Process, and Infrastructure for all three hospitals. TeATH is a simple and generic tool that provides decision support and guidance to health planners, differentiating weak or lagging implementations for which remedial action can be introduced. The tool has been adopted by the Provincial Department of Health, and has already influenced recent policy decisions. Broad application of TeATH would reduce wasteful expenditure, and facilitate implementation and uptake of telehealth in South Africa and elsewhere

Establishing a pharmacist–prescriber partnership in publicly funded primary healthcare clinics to optimisantibiotic prescribing in the Western Cape: An exploratory study

Promoting evidence-based antibiotic prescribing through successful antimicrobial stewardship (AMS) programmes is critical to preserving the effectiveness of antibiotics for common infections in primary care. This requires a coordinated multidisciplinary effort. Such pharmacist–prescriber partnerships have been effective in high-income countries (HICs). Yet, evidence generated in such countries is not always applicable because of different social determinants of health. Methods: A multidisciplinary workshop was conducted with pharmacists and clinicians (doctors, nurses) on community-based antibiotic stewardship, the purpose of which was to explore how and where such partnerships might work in publicly funded primary care clinics in the greater Cape Metro region. Results: Participants perceived that promoting effective AMS was a priority for South African primary healthcare. However, it was clear that there are many hurdles to overcome working in settings that are relatively resource-poor. Prescribing guidelines needed to be harmonised. Participants felt that staff training on the principles of AMS should be mandatory

Comparative embryotoxicity of a pentabrominated diphenyl ether mixture to common terns (\u3ci\u3eSterna hirundo\u3c/i\u3e) and American kestrels (\u3ci\u3eFalco sparverius\u3c/i\u3e)

Concentrations of polybrominated diphenyl ethers (PBDEs) in Forster’s tern (Sterna forsteri) eggs from San Francisco Bay have been reported to range up to 63 µg g-1 lipid weight. This value exceeds the lowest-observed-adverse-effect level (1.8 µg g-1 egg wet weight; ~32 µg g-1 lipid weight) reported in an embryotoxicity study with American kestrels (Falco sparverius). As a surrogate for Forster’s terns, common tern (Sterna hirundo) eggs were treated by air cell injection with corn oil vehicle (control) or a commercial penta-BDE formulation (DE-71) at nominal concentrations of 0.2, 2, and 20 µg g-1 egg. As a positive control, kestrel eggs received vehicle or 20 µg DE-71 g-1 egg. In terns, there were no effects of DE-71 on embryonic survival, and pipping or hatching success; however, treated eggs hatched later (0.44 d) than controls. Organ weights, organ-to-body weight ratios, and bone lengths did not differ, and histopathological observations were unremarkable. Several measures of hepatic oxidative stress in hatchling terns were not affected by DE-71, although there was some evidence of oxidative DNA damage (8-hydroxy-deoxyguanosine; 8-OH-dG). Although DE-71 did not impair pipping and hatching of kestrels, it did result in a delay in hatch, shorter humerus length, and reduced total thyroid weight. Concentrations of oxidized glutathione, reduced glutathione, thiobarbituric acid reactive substances, and 8-OH-dG in liver were greater in DE-71-treated kestrels compared to controls. Our findings suggest common tern embryos, and perhaps other tern species, are less sensitive to PBDEs than kestrel embryos

The proteome of Nicotiana benthamiana is shaped by extensive protein processing

Summary: Processing by proteases irreversibly regulates the fate of plant proteins and hampers the production of recombinant proteins in plants, yet only few processing events have been described in agroinfiltrated Nicotiana benthamiana, which has emerged as the main transient protein expression platform in plant science and molecular pharming. Here, we used in‐gel digests and mass spectrometry to monitor the migration and topography of 5040 plant proteins within a protein gel. By plotting the peptides over the gel slices, we generated peptographs that reveal where which part of each protein was detected within the protein gel. These data uncovered that 60% of the detected proteins have proteoforms that migrate at lower than predicted molecular weights, implicating extensive proteolytic processing. This analysis confirms the proteolytic removal and degradation of autoinhibitory prodomains of most but not all proteases, and revealed differential processing within pectinemethylesterase and lipase families. This analysis also uncovered intricate processing of glycosidases and uncovered that ectodomain shedding might be common for a diverse range of receptor‐like kinases. Transient expression of double‐tagged candidate proteins confirmed processing events in vivo. This large proteomic dataset implicates an elaborate proteolytic machinery shaping the proteome of N. benthamiana

Cytokines genotypes as predictors of disease outcomes in HIV-1 infected Ukrainians

У тезах представлені дані щодо асоціації поліморфізмів генів цитокінів з опортуністичними інфекціями у українців з ВІЛ-1.В тезисах представлены данные об ассоциации полиморфизмов генов цитокинов с оппортунистическими инфекциями у украинцев с ВИЧ-1.The data of cytokines genotypes association with outcomes of the disease in Ukrainians with HIV-1 were presented

Post-Translational Regulation and Trafficking of the Granulin-Containing Protease RD21 of Arabidopsis thaliana

RD21-like proteases are ubiquitous, plant-specific papain-like proteases typified by carrying a C-terminal granulin domain. RD21-like proteases are involved in immunity and associated with senescence and various types of biotic and abiotic stresses. Here, we interrogated Arabidopsis RD21 regulation and trafficking by site-directed mutagenesis, agroinfiltration, western blotting, protease activity profiling and protein degradation. Using an introduced N-glycan sensor, deglycosylation experiments and glyco-engineered N. benthamiana plants, we show that RD21 passes through the Golgi where it becomes fucosylated. Our studies demonstrate that RD21 is regulated at three post-translational levels. Prodomain removal is not blocked in the catalytic Cys mutant, indicating that RD21 is activated by a proteolytic cascade. However, RD21 activation in Arabidopsis does not require vacuolar processing enzymes (VPEs) or aleurain-like protease AALP. In contrast, granulin domain removal requires the catalytic Cys and His residues and is therefore autocatalytic. Furthermore, SDS can (re-)activate latent RD21 in Arabidopsis leaf extracts, indicating the existence of a third layer of post-translational regulation, possibly mediated by endogenous inhibitors. RD21 causes a dominant protease activity in Arabidopsis leaf extracts, responsible for SDS-induced proteome degradation

Characterization of Polyphosphoesters by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

FT-ICR mass spectrometry, together with collision-induced dissociation and electron capture dissociation, has been used to characterize the polyphosphoester poly[1,4-bis(hydroxyethyl)terephthalate-alt-ethyloxyphosphate] and its degradation products. Three degradation pathways were elucidated: hydrolysis of the phosphate–[1,4-bis(hydroxyethyl)terephthalate]bonds; hydrolysis of the phosphate–ethoxy bonds; and hydrolysis of the ethyl–terephthalate bonds. The dominant degradation reactions were those that involved the phosphate groups. This work constitutes the first application of mass spectrometry to the characterization of polyphosphoesters and demonstrates the suitability of high mass accuracy FT-ICR mass spectrometry, with CID and ECD, for the structural analysis of polyphosphoesters and their degradation products