A vaccine displaying a trimeric influenza-A HA stem protein on capsid-like particles elicits potent and long-lasting protection in mice

Due to constant antigenic drift and shift, current influenza-A vaccines need to be redesigned and administered annually. A universal flu vaccine (UFV) that provides long-lasting protection against both seasonal and emerging pandemic influenza strains is thus urgently needed. The hemagglutinin (HA) stem antigen is a promising target for such a vaccine as it contains neutralizing epitopes, known to induce cross-protective IgG responses against a wide variety of influenza subtypes. In this study, we describe the development of a UFV candidate consisting of a HAstem trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HAstem trimer, the CLP-HAstem particles induced a more potent, long-lasting immune response and were able to protect mice against both homologous and heterologous H1N1 influenza challenge, even after a single dose

Rheumatoid arthritis, gold therapy, contact allergy and blood cytokines

OBJECTIVE: To study the clinical and biochemical effects of a low starting dose for gold therapy in rheumatoid arthritis patients with a contact allergy to gold. METHODS: Serum cytokines were assayed before and 24 h after the first injection of gold sodium thiomalate (GSTM). RESULTS: Contact allergy to gold was found in 4 of 19 patients. Compared to gold-negative patients (starting dose: 10 mg GSTM), there was a larger increase in serum TNFalpha (p < 0.05), sTNF-R1 (NS), and IL-1 ra (p < 0.05) in gold-allergic patients. CONCLUSIONS: Cytokines are released in blood by GSTM in RA patients with gold allergy. To minimize the risk of acute adverse reactions the starting dose of GSTM should be lowered to 5 mg. Alternatively, patients should be patch-tested before gold therapy; in test-positive cases, 5 mg is recommended as the first dose

Sensing of Fatty Acids for Octanoylation of Ghrelin Involves a Gustatory G-Protein

Ghrelin is an important regulator of energy--and glucose homeostasis. The octanoylation at Ser(3) is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell.Wild-type (WT) and α-gustducin knockout (gust(-/-)) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo.Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/-) mice. Gastric emptying was accelerated in WT but not in gust(-/-) mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels.This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell

Changes in bone mineral density over 10 years in patients with early rheumatoid arthritis

Objectives To investigate changes in bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) over a 10-year period. Methods Consecutive patients with early RA (symptom duration <12 months) were followed according to a structured programme and examined with dual-energy X-ray absorptiometry (DXA) at inclusion and after 2, 5 and 10 years. Mean Z-scores over the study period were estimated using mixed linear effect models. Changes in Z-scores between follow-up visits were analysed using paired T-tests. Results At inclusion, 220 patients were examined with DXA. At the femoral neck, the mean Z-score over 10 years was -0.33 (95 % CI -0.57 to -0.08) in men and -0.07 (-0.22 to 0.08) in women. Men had significantly lower BMD at the femoral neck than expected by age at inclusion (intercept Z-score value -0.35; 95 % CI -0.61 to -0.09), whereas there was no such difference in women. At the lumbar spine, the mean Z-score over the study period for men was -0.05 (-0.29 to 0.19) and for women 0.06 (-0.10 to 0.21). In paired comparisons of BMD at different follow-up visits, femoral neck Z-scores for men decreased significantly from inclusion to the 5-year follow-up. After 5 years, no further reduction was seen. Conclusions In this observational study of a limited sample, men with early RA had reduced femoral neck BMD at diagnosis, with a further significant but marginal decline during the first 5 years. Lumbar spine BMD Z-scores were not reduced in men or women with early RA. Data on 10-year follow-up were limited

The Nurse Professional Competence (NPC) scale : self-reported competence among nursing students on the point of graduation

BACKGROUND: International organisations, e.g. WHO, stress the importance of competent registered nurses (RN) for the safety and quality of healthcare systems. Low competence among RNs has been shown to increase the morbidity and mortality of inpatients. OBJECTIVES: To investigate self-reported competence among nursing students on the point of graduation (NSPGs), using the Nurse Professional Competence (NPC) Scale, and to relate the findings to background factors. METHODS AND PARTICIPANTS: The NPC Scale consists of 88 items within eight competence areas (CAs) and two overarching themes. Questions about socio-economic background and perceived overall quality of the degree programme were added. In total, 1086 NSPGs (mean age, 28.1 [20-56]years, 87.3% women) from 11 universities/university colleges participated. RESULTS: NSPGs reported significantly higher scores for Theme I "Patient-Related Nursing" than for Theme II "Organisation and Development of Nursing Care". Younger NSPGs (20-27years) reported significantly higher scores for the CAs "Medical and Technical Care" and "Documentation and Information Technology". Female NSPGs scored significantly higher for "Value-Based Nursing". Those who had taken the nursing care programme at upper secondary school before the Bachelor of Science in Nursing (BSN) programme scored significantly higher on "Nursing Care", "Medical and Technical Care", "Teaching/Learning and Support", "Legislation in Nursing and Safety Planning" and on Theme I. Working extra paid hours in healthcare alongside the BSN programme contributed to significantly higher self-reported scores for four CAs and both themes. Clinical courses within the BSN programme contributed to perceived competence to a significantly higher degree than theoretical courses (93.2% vs 87.5% of NSPGs). SUMMARY AND CONCLUSION: Mean scores reported by NSPGs were highest for the four CAs connected with patient-related nursing and lowest for CAs relating to organisation and development of nursing care. We conclude that the NPC Scale can be used to identify and measure aspects of self-reported competence among NSPGs