Advanced Access scheduling in general practice and use of primary care: a Danish population-based matched cohort study.

BACKGROUND: Advanced access scheduling (AAS) allows patients to receive care from their GP at the time chosen by the patient. AAS has shown to increase the accessibility to general practice, but little is known about how AAS implementation affects the use of in-hours and out-of-hours (OOH) services. AIM: To describe the impact of AAS on the use of in-hours and OOH services in primary care. DESIGN & SETTING: A population-based matched cohort study using Danish register data. METHOD: A total of 161 901 patients listed in 33 general practices with AAS were matched with 287 837 reference patients listed in 66 reference practices without AAS. Outcomes of interest were use of daytime face-to-face consultations, and use of OOH face-to-face and phone consultations in a 2-year period preceding and following AAS implementation. RESULTS: No significant differences were seen between AAS practices and reference practices. During the year following AAS implementation, the number of daytime face-to-face consultations was 3% (adjusted incidence rate ratio [aIRR] = 1.03; 95% confidence interval [CI] = 0.99 to 1.07) higher in the AAS practices compared with the number in the reference practices. Patients listed with an AAS practice had 2% (aIRR = 0.98; 95% CI = 0.92 to 1.04) fewer OOH phone consultations and 6% (aIRR = 0.94; 95% CI = 0.86 to 1.02) fewer OOH face-to-face consultations compared with patients listed with a reference practice. CONCLUSION: This study showed no significant differences following AAS implementation. However, a trend was seen towards slightly higher use of daytime primary care and lower use of OOH primary care.

Insulin fibrillation: The influence and coordination of Zn2.

Protein amyloid fibrillation is obtaining much focus because it is connected with amyloid-related human diseases such as Alzheimer's disease, diabetes mellitus type 2, or Parkinson's disease. The influence of metal ions on the fibrillation process and whether it is implemented in the amyloid fibrils has been debated for some years. We have therefore investigated the influence and binding geometry of zinc in fibrillated insulin using extended X-ray absorption fine-structure and X-ray absorption near-edge structure spectroscopy. The results were validated with fibre diffraction, Transmission Electron Microscopy and Thioflavin T fluorescence measurements. It is well-known that Zn2+ ions coordinate and stabilize the hexameric forms of insulin. However, this study is the first to show that zinc indeed binds to the insulin fibrils. Furthermore, zinc influences the kinetics and the morphology of the fibrils. It also shows that zinc coordinates to histidine residues in an environment, which is similar to the coordination seen in the insulin R6 hexamers, where three histidine residues and a chloride ion is coordinating the zinc.

The structure of Lactococcus lactis thioredoxin reductase reveals molecular features of photo-oxidative damage.

The NADPH-dependent homodimeric flavoenzyme thioredoxin reductase (TrxR) provides reducing equivalents to thioredoxin, a key regulator of various cellular redox processes. Crystal structures of photo-inactivated thioredoxin reductase (TrxR) from the Gram-positive bacterium Lactococcus lactis have been determined. These structures reveal novel molecular features that provide further insight into the mechanisms behind the sensitivity of this enzyme toward visible light. We propose that a pocket on the si-face of the isoalloxazine ring accommodates oxygen that reacts with photo-excited FAD generating superoxide and a flavin radical that oxidize the isoalloxazine ring C7α methyl group and a nearby tyrosine residue. This tyrosine and key residues surrounding the oxygen pocket are conserved in enzymes from related bacteria, including pathogens such as Staphylococcus aureus. Photo-sensitivity may thus be a widespread feature among bacterial TrxR with the described characteristics, which affords applications in clinical photo-therapy of drug-resistant bacteria.