Medlinlundgreen4929
The role of receptor activity-modifying proteins (RAMPs) in modulating the pharmacological effects of an amylin receptor selective agonist (NN1213) or the dual amylin-calcitonin receptor agonist (DACRA), salmon calcitonin (sCT), was tested in three RAMP KO mouse models, RAMP1, RAMP3 and RAMP1/3 KO. Male wild-type (WT) and knockout (KO) littermate mice were fed a 45% high-fat diet for 20 weeks prior to the 3-week treatment period. A decrease in body weight after NN1213 was observed in all WT mice, whereas sCT had no effect. The absence of RAMP1 had no significant effect on NN1213 efficacy, and sCT was still inactive. However, the absence of RAMP3 impeded NN1213 efficacy but improved sCT efficacy. Similar results were observed in RAMP1/3 KO suggesting that the amylin receptor 3 (AMY3 = CTR + RAMP3) is necessary for NN1213's maximal action on body weight and food intake and that the lack of AMY3 allowed sCT to be active. These results suggest that the chronic use of DACRA such as sCT can have unfavourable effect on body weight loss in mice (which differs from the situation in rats), whereas the use of the amylin receptor selective agonist does not. AMY3 seems to play a crucial role in modulating the action of these two compounds, but in opposite directions. The assessment of a long-term effect of amylin and DACRA in different rodent models is necessary to understand potential physiological beneficial and unfavourable effects on weight loss before its transition to clinical trials.
Ceftazidime (CAZ) solutions are being used based on anecdotal reports for otitis externa complicated by multidrug-resistant Pseudomonas aeruginosa (MDR PA). The chemical and microbiological stability of these proposed compounded solutions have not been evaluated, and likely are affected by the diluent and storage duration or temperature.
Compounded CAZ solutions would show variable degradation dependent on diluent, time and temperature. The antimicrobial activity of the solutions would reflect changes in concentration and not alterations to the chemical compound.
Ceftazidime was compounded with 100mL 0.9% sodium chloride (NA+CAZ), 118mL Triz-EDTAAqueous flush (TE+CAZ) and 125mL Douxo Micellar Solution (MI+CAZ). Aliquots of the solutions were stored at 25ºC, 4ºC and -20ºC for 28 days. High-performance liquid chromatography was used to analyse CAZ recovery from compounded solutions at weekly intervals. A modified broth dilution technique was utilised to assess minimum inhibitory concentration (MIC) to monitor antimicrobial activity against a reference PA strain.
Temperature, duration of storage and diluent each had independent effects on the chemical stability of CAZ. CAZ concentrations decreased over time as well as with increased temperature. NA+CAZ solutions exhibited the least degradation compared to the other solutions. The MIC for PA was most consistent for NA+CAZ solutions regardless of storage temperature and duration of storage.
Chemical and microbiological stability of compounded CAZ solutions varied by diluent, storage temperature and duration of storage. Cyclopamine Smoothened antagonist Dilution in NA resulted in the lowest variation in stability over 28 days when stored at refrigerated or frozen temperatures compared to other diluents.
Chemical and microbiological stability of compounded CAZ solutions varied by diluent, storage temperature and duration of storage. Dilution in NA resulted in the lowest variation in stability over 28 days when stored at refrigerated or frozen temperatures compared to other diluents.Rhododendrons are woody plants, famous throughout the world as having high horticultural value. However, many wild species are currently threatened with extinction. Here, we report for the first time a high-quality, chromosome-level genome of Rhododendron griersonianum, which has contributed to approximately 10% of all horticultural rhododendron varieties but which in its wild form has been evaluated as critically endangered. The final genome assembly, which has a contig N50 size of approximately 34 M and a total length of 677 M, is the highest-quality genome sequenced within the genus to date, in part due to its low heterozygosity (0.18%). Identified repeats constitute approximately 57% of the genome, and 38 280 protein-coding genes were predicted with high support. We further resequenced 31 individuals of R. griersonianum as well as 30 individuals of its widespread relative R. delavayi, and performed additional conservation genomic analysis. The results showed that R. griersonianum had lower genetic diversind in the genus Rhododendron in general.
The Australian Treatment Outcomes Profile (ATOP) is a brief instrument that measures self-reported substance use, health, and wellbeing in the previous 28 days for people in alcohol and other drug treatment. Previous studies have established the concurrent validity, inter-rater, and test-retest reliability of the tool. The current study sought to identify recommended cutoff scores for ATOP items for psychological health, physical health and quality of life that identify clients reporting clinically significant problems warranting further assessment and/or intervention, compared to cutoffs used by 'gold-standard' measures for these domains.
Clients attending for treatment for problems with opioid (n= 144) or alcohol use (n= 134) completed the ATOP and comparison standardised questionnaires (Kessler-10, Short Form Survey 12 and the Personal Wellbeing Index) with a researcher. Receiver operating characteristics analysis, along with clinician perspectives, were used to recommend cutoff scores for ATOP items indicative of clinically significant problems.
A cutoff score of 5 or less out of 10 was identified as an optimal pragmatic cutoff for ATOP items relating to psychological health, physical health and quality of life items with regards to balancing sensitivity, specificity, and application in a treatment setting.
The recommended clinical cutoffs will support clinicians and treatment services to identify clients who require further assessment and follow up for their psychological health, physical health and quality of life. The current study provides further evidence for the utility of the ATOP for individual clinical review, service planning and research.
The recommended clinical cutoffs will support clinicians and treatment services to identify clients who require further assessment and follow up for their psychological health, physical health and quality of life. The current study provides further evidence for the utility of the ATOP for individual clinical review, service planning and research.
