A growth type pathway for improving the folding of BPTI.

The in vitro oxidative folding of the protein bovine pancreatic trypsin inhibitor (BPTI) with oxidized dithiothreitol or glutathione has served as a paradigm for protein folding but could take weeks at physiological pH because of the need to escape from kinetic traps via a rearrangement type pathway. The two major kinetic traps are called N' and N* and contain two of the three native disulfide bonds, which occur between residues 5 and 55, 30 and 51, and 14 and 38. N' is missing the disulfide bond between residues 5 and 55 while N* is missing the disulfide bond between residues 30 and 51. By determining rate constant for the reactions of the kinetic traps N* and N' and their mixed disulfides with glutathione and glutathione disulfide, many for the first time, we demonstrate that growth type pathways are feasible and could even be more efficient than rearrangement type pathways. Thus, formally unproductive pathways became productive. Interestingly, under physiological redox conditions both rearrangement and growth type pathways are important highlighting the redundancy of oxidative protein folding. With the new set of rate constants, modeling indicated that in vitro oxidative protein folding of BPTI via a growth type pathway using an oxidation, reduction and oxidation cycle would significantly improve protein folding efficiency, albeit under non-physiological redox conditions. With these changing conditions 91 ± 2% of native BPTI was achieved in 12 h compared to 83% native protein in 24 h using our previous best conditions of 5 mM GSSG and 5 mM GSH. Therefore, changing redox conditions via an oxidation, reduction and oxidation cycle may become an additional methodology for enhancing in vitro protein folding in aqueous solution.

Risk Factors for Deterioration Events in the Pediatric Acute Care Setting.

OBJECTIVES: Rapid response system (RRS) activations resulting in emergency transfers (ETs) and codes outside the ICU are associated with increased mortality and length of stay. We aimed to evaluate the patient and care team characteristics of RRS activations resulting in ETs and codes outside the ICU (together classified as "deterioration events") versus those that did not result in a deterioration event. METHODS: For each RRS activation at our institution from 2019 to 2021, data were gathered on patient demographics and medical diagnoses, care team and treatment factors, and ICU transfer. Descriptive statistics, bivariate analyses, and multivariable logistic regression using a backward elimination model selection method were performed to assess potential risk factors for deterioration events. RESULTS: Over the 3-year period, 1765 RRS activations were identified. Fifty-three (3%) activations were deemed acute care codes, 64 (4%) were noncode ETs, 921 (52%) resulted in nonemergent transfers to an ICU, and 727 (41%) patients remained in an acute care unit. In a multivariable model, any complex chronic condition (adjusted odds ratio, 6.26; 95% confidence interval, 2.83-16.60) and hematology/oncology service (adjusted odds ratio, 2.19; 95% confidence interval, 1.28-3.74) were independent risk factors for a deterioration event. CONCLUSIONS: Patients with medical complexity and patients on the hematology/oncology service had a higher risk of deterioration events than other patients with RRS activations. Further analyzing how our hospital evaluates and treats these specific patient populations is critical as we develop targeted interventions to reduce deterioration events.

Benchmarking non-attendance patterns in paediatric medical imaging: A retrospective cohort study spotlighting First Nations children.

INTRODUCTION: Non-attendance at Medical Imaging (MI) appointments can result in inefficiencies in healthcare resource allocation, increased financial burdens, and lead to potential barriers to effective healthcare delivery. We evaluated factors associated with non-attendance of MI appointments for children including variables: gender; age groups; residential postcodes; Indigenous status; appointment dates; appointment reminders and socio-economic status. METHOD: Retrospective cohort study of children with scheduled MI appointments at a Tertiary paediatric hospital in Australia, between January and December 2022. Data were extracted from the Radiology Information System and integrated with socio-economic census data through linking with postcode. Chi-squared, and logistic regression analysis were performed to identify significant predictors of non-attendance. RESULTS: Out of 17,962 scheduled outpatient appointments, 6.2 % did not attend. Males were less likely to attend than females (7.3 % vs. 5.8 %; p < 0.001). Older children had the highest frequency of non-attendance (p < 0.001). First Nations identified children had a higher likelihood of non-attendance at 14.5 % compared to non-First Nations at 5.8 %, and the odds ratio (OR) of First Nation children not attending was 2.54 (CI 2.13-3.03; p < 0.001) higher than non-First Nations children. Children from areas of disadvantage were less likely to attend (p < 0.001). Bone mineral densitometry had the highest odds of non-attendance (19.4 % of bookings) compared to other imaging modalities (p < 0.001). CONCLUSION: The following characteristics were associated with non-attendance: older male gender, residing in areas of socio-economic disadvantage, or identifying as First Nations Australians. By reviewing these findings with the cultural and professional experience of our Indigenous co-author, we have identified some strategies for improving attendance amongst First Nations children. IMPLICATIONS FOR PRACTICE: Factors associated with non-attendance, or "missed opportunities for care", provide opportunities for intervention to improve attendance for vulnerable groups of children who require medical imaging.