Adsorption and Leachable Contamination of Flucloxacillin, Cyclosporin and Amiodarone Following Delivery Through an Intravenous Administration Set.

PURPOSE: Interactions between a pharmaceutical drug and its delivery device can result in changes in drug concentration and leachable contamination. Flucloxacillin, amiodarone and cyclosporin were investigated for drug concentration changes and leachable contamination after delivery through an intravenous administration set. METHODS: Flucloxacillin, amiodarone and cyclosporin were delivered through an intravenous administration set and the eluate analysed by HPLC-UV and HPLC-MS. RESULTS: The average recovery of flucloxacillin was 99.7% and no leachable compounds were identified. The average recovery of cyclosporin was 96.1%, which contrasts previous findings that have reported up to 50% loss of cyclosporin. This is likely due to the use of DEHP-free administration sets in this study, as adsorption of cyclosporin is linearly related to DEHP content. The average recovery of amiodarone was 91.5%. 5-hydroxymethylfurfural was identified in the amiodarone solution following delivery through the administration set as well as the 5% glucose solution used for delivery. CONCLUSIONS: Drug/administration set interactions may modify pharmaceuticals during delivery. In this study, only 90% of the amiodarone was delivered through a generic administration set. Given the growing use of generic administration sets in hospital settings, validation of the suitability of their use is required to ensure patient safety and expected levels of efficacy.

Assessment of the Detrimental Impact of Polyvalent Streptophages Intended to be Used as Biological Control Agents on Beneficial Soil Streptoflora.

Streptophages are currently being investigated to control potato common scab, however, since a majority of streptophages are reported to be polyvalent, their potential to infect beneficial soil streptomycetes during the application process may have unintended consequences. To test this hypothesis, two phytopathogenic fungi, namely Fusarium solani and Rhizoctonia solani, were tested for their detrimental effect on the test crop wheat (Triticum aestivum cv. Gutha). F. solani caused a significant root weight reduction (34%) in the wheat plant and therefore was tested further in the pot trials with actinomycetes present. Sixty-seven streptomycete isolates from a Tasmanian potato farm were screened for their antifungal abilities against the two phytopathogenic fungi. Four actinomycetes found to be strongly antifungal were then tested for their disease-protective abilities against F. solani in pot trials again using wheat. Addition of the streptomycetes into the container media protected the plants against F. solani, indicating that streptomycetes have a disease-suppressive effect. A further pot trial was conducted to evaluate whether these beneficial streptomycete species would be affected by streptophage treatment and subsequently result in an increased risk of fungal infections. When streptophages were added to the pots, the shoot and root growth of wheat declined by 23.6% and 8.0%, respectively, in the pots with the pathogenic fungus compared to the control pots. These differences might suggest that removal of antifungal streptomycetes by polyvalent phages from plant rhizosphere when biocontrol of plant pathogenic streptomycetes (e.g. Streptomyces scabiei) is targeted might encourage secondary fungal infections in the farm environment. The presented data provide preliminary evidence that streptophage treatment of pathogenic streptomycetes may lead to an aggravated disease risk by soil-borne fungal pathogens when naturally present antagonists are removed. As a result, extensive farm site trials are required to determine the long-term detrimental impact of polyvalent streptophage treatments on beneficial soil streptoflora.

Sumoylation differentially regulates Sp1 to control cell differentiation.

The mammalian small ubiquitin-like modifiers (SUMOs) are actively involved in regulating differentiation of different cell types. However, the functional differences between SUMO isoforms and their mechanisms of action remain largely unknown. Using the ocular lens as a model system, we demonstrate that different SUMOs display distinct functions in regulating differentiation of epithelial cells into fiber cells. During lens differentiation, SUMO1 and SUMO2/3 displayed different expression, localization, and targets, suggesting differential functions. Indeed, overexpression of SUMO2/3, but not SUMO1, inhibited basic (b) FGF-induced cell differentiation. In contrast, knockdown of SUMO1, but not SUMO2/3, also inhibited bFGF action. Mechanistically, specificity protein 1 (Sp1), a major transcription factor that controls expression of lens-specific genes such as ß-crystallins, was positively regulated by SUMO1 but negatively regulated by SUMO2. SUMO2 was found to inhibit Sp1 functions through several mechanisms: sumoylating it at K683 to attenuate DNA binding, and at K16 to increase its turnover. SUMO2 also interfered with the interaction between Sp1 and the coactivator, p300, and recruited a repressor, Sp3 to ß-crystallin gene promoters, to negatively regulate their expression. Thus, stable SUMO1, but diminishing SUMO2/3, during lens development is necessary for normal lens differentiation. In support of this conclusion, SUMO1 and Sp1 formed complexes during early and later stages of lens development. In contrast, an interaction between SUMO2/3 and Sp1 was detected only during the initial lens vesicle stage. Together, our results establish distinct roles of different SUMO isoforms and demonstrate for the first time, to our knowledge, that Sp1 acts as a major transcription factor target for SUMO control of cell differentiation.

Impact of Pharmacist Interventions at an Outpatient US Coast Guard Clinic.

Background: US Coast Guard (USCG) active-duty service members (ADSMs) are required to maintain medical readiness to maximize operational success. USCG pharmacists serve the traditional pharmacist role while maintaining oversight of regional pharmaceutical services. This study aimed to quantify the number, duty status impact, and replicability of medication interventions made by one pharmacist at the USCG Base Alameda clinic in California over 6 months. Methods: Medication interventions made at the USCG Base Alameda clinic from July 1, 2021, to December 31, 2021, were categorized as a drug therapy problem (DTP) or non-DTP. Each DTP was further evaluated in a retrospective record review by a panel of USCG pharmacists to assess 2 additional factors: duty status severity (potential to affect duty status) and replicability (potential for the same intervention to be made in the absence of access to the patient health record). Results: USCG Base Alameda pharmacy dispensed 1751 prescriptions and made 116 interventions (7%), of which 111 (96%) were accepted by the prescriber. Of the interventions, 64 (55%) were DTPs, and 14 of those (22%) had potential to change duty status, and 18 DTPs (28%) were made because the pharmacist had access to the health record. Conclusions: Pharmacists' role in USCG clinics includes collaborating with the patient care team to make medication interventions that have significant impact on ADSMs' wellness and the USCG mission.

Intracranial sclerosing extramedullary haematopoietic tumour mimicking meningioma in a patient with myelofibrosis: Case report.

Sclerosing extramedullary hematopoietic tumour is a rare tumour which can occur in certain myeloproliferative diseases, typically myelofibrosis. Typically these tumours present as a discrete retroperitoneal mass or masses, however they can occur in other sites within the body. In this case report we describe a 61-year old woman who underwent stealth guided bi-temporal craniotomy for resection of what was expected to be a large falx meningioma, however histopathology revealed the lesion to be a sclerosing extramedullary hematopoietic tumour. Following surgery, the patients post-operative recovery was complicated by intracerebral haemorrhage which required emergency evacuation and the patient remained in intensive care on a ventilator for 3 weeks. At one year follow up the patient reports her presenting symptoms of headaches, nausea, and vertigo had resolved.

Bioactive Streptomycetes from Isolation to Applications: A Tasmanian Potato Farm Example.

The genus Streptomyces constitutes approximately 50% of all soil actinomycetes, playing a significant role in the soil microbial community through vital functions including nutrient cycling, production of bioactive metabolites, disease-suppression and plant growth promotion. Streptomyces produce many bioactive compounds and are prime targets for industrial and biotechnological applications. In addition to their agrobiological roles, some Streptomyces spp. can, however, be phytopathogenic, examples include, common scab of potato that causes economic losses worldwide. Currently used chemical control measures can have detrimental effect to environmental and human health as a result alternative methods to chemical disease control are being investigated. One alternative is the use of streptomycete specific phages to remove this pathogenic bacterium before it can cause the disease on potatoes. However, due to co-existence of non-common scab-causing species belonging to the genus Streptomyces, phage treatment is likely to affect a wide range of non-target streptomycete species including the beneficial ones in the soil. Therefore, before such treatment starts the host range of the phages within the targeted family of bacteria should be determined. In a study conducted using soil samples from a Tasmanian potato farm, streptomycetes were isolated and tested against streptomycete-specific phages. Their antifungal activity was also determined using multiple assays against selected phytopathogens. The four strongest antifungal activity-displaying isolates were further tested for their persistent antifungal activity using wheat and Fusarium solani in a pot trial. A second pot trial was also conducted to evaluate whether the beneficial streptomycetes were affected by streptophage treatment and whether their removal via the phage battery would cause opportunistic fungal infections to plants in soil. The streptomycetes prevented the reduction in wheat shoot weight caused by F. solani indicating their disease suppressive effect. However, when phages were added into the pots, the growth of wheat was detrimentally impacted. This finding might suggest that the reduced presence of antifungal streptomycetes via phage-induced lysis might encourage opportunistic fungal infections in plants.

Safety of Non-Operating Room Anesthesia: A Closed Claims Update.

Malpractice claims for non-operating room anesthesia care (NORA) had a higher proportion of claims for death than claims in operating rooms (ORs). NORA claims most frequently involved monitored anesthesia care. Inadequate oxygenation/ventilation was responsible for one-third of NORA claims, often judged probably preventable by better monitoring. Fewer malpractice claims for NORA occurred than for OR anesthesia as assessed by the relative numbers of in NORA versus OR procedures. The proportion of claims in cardiology and radiology NORA locations were increased compared with estimates of cases in these locations. Although NORA is safe, adherence to safe clinical practice is important.