Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor

Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits. We found that the proteasome mutants are multi-drug resistant due to stabilization of the stress-activated transcription factor Pap1. We show that the ubiquitylation and ultimately the degradation of Pap1 depend on the Rhp6/Ubc2 E2 ubiquitin conjugating enzyme and the Ubr1 E3 ubiquitin-protein ligase. Accordingly, mutants lacking Rhp6 or Ubr1 display drug-resistant phenotypes

Short anterior correction of the thoracolumbar/lumbar curve in King 1 idiopathic scoliosis: the behaviour of the instrumented and non-instrumented curves and the trunk balance

This is a retrospective clinical, radiological and patient outcome assessment of 21 consecutive patients with King 1 idiopathic adolescent scoliosis treated by short anterior selective fusion of the major thoracolumbar/lumbar (TL/L) curve. Three-dimensional changes of both curves, changes in trunk balance and rib hump were evaluated. The minimal follow-up was 24 months (max. 83). The Cobb angle of the TL/L curve was 52° (45–67°) with a flexibility of 72% (40–100%). The average length of the main curve was 5 (3–8) segments. An average of 3 (2–4) segments was fused using rigid single rod implants with side-loading screws. The Cobb angle of the thoracic curve was 33° (18–50°) with a flexibility of 69% (29–100%). The thoracic curve in bending was less than 20° in 17 patients, and 20–25° in 4 patients. In the TL/L curve there was an improvement of the Cobb angle of 67%, of the apex vertebral rotation of 51% and of the apex vertebral translation of 74%. The Cobb angle of the thoracic curve improved 29% spontaneously. Shoulder balance improved significantly from an average preoperative imbalance of 14.5–3.1 mm at the last follow-up. Seventy-five percent of the patients with preoperative positive shoulder imbalance (higher on the side of the thoracic curve) had levelled shoulders at the last follow-up. C7 offset improved from a preoperative 19.8 (0–40) to 4.8 (0–18) mm at the last follow-up. There were no significant changes in rotation, translation of the thoracic curve and the clinical rib hump. There were no significant changes in thoracic kyphosis or lumbar lordosis. The average score of the SRS-24 questionnaire at the last follow-up was 91 points (max. 120). We conclude that short anterior selective fusion of the TL/L curve in King 1 scoliosis with a thoracic curve bending to 25° or less (Type 5 according to Lenke classification) results in a satisfactory correction and a balanced spine. Short fusions leave enough mobile lumbar segments for the establishment of global spinal balance. A positive shoulder imbalance is not a contraindication for this procedure. Structural interbody grafts are not necessary to maintain lumbar lordosis

Determinants of outpatient expenditure within primary care in the Brazilian National Health System

ABSTRACT CONTEXT AND OBJECTIVE: One of the big challenges facing governments worldwide is the financing of healthcare systems. Thus, it is necessary to understand the factors and key components associated with healthcare expenditure. The aim here was to identify demographic, socioeconomic, lifestyle and clinical factors associated with direct healthcare expenditure within primary care, among adults attended through the Brazilian National Health System in the city of Bauru. DESIGN AND SETTING: Cross-sectional study conducted in five primary care units in Bauru (SP), Brazil. METHODS: Healthcare expenditure over the last 12 months was assessed through medical records of adults aged 50 years or more. Annual healthcare expenditure was assessed in terms of medication, laboratory tests, medical consultations and the total. Body mass index, waist circumference, hypertension, age, sex, physical activity and smoking were assessed through face-to-face interviews. RESULTS: The total healthcare expenditure for 963 participants of this survey was US$ 112,849.74 (46.9% consultations, 35.2% medication and 17.9% laboratory tests). Expenditure on medication was associated with overweight (odds ratio, OR = 1.80; 95% confidence interval, CI: 1.07-3.01), hypertension (OR = 3.04; 95% CI: 1.91-4.82) and moderate physical activity (OR = 0.56; 95% CI: 0.38-0.81). Expenditure on consultations was associated with hypertension (OR = 1.67; 95% CI: 1.12-2.47) and female sex (OR = 1.70; 95% CI: 1.14-2.55). CONCLUSIONS: Our results showed that overweight, lower levels of physical activity and hypertension were independent risk factors associated with higher healthcare expenditure within primary care