Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated with systemic and intramuscular lipid metabolism:Role of HIV lipodystrophy

Interleukin (IL)-18 is involved in regulation of lipid and glucose metabolism. Mice lacking whole-body IL-18 signalling are prone to develop weight gain and insulin resistance, a phenotype which is associated with impaired fat oxidation and ectopic skeletal muscle lipid deposition. IL-18 mRNA is expressed in human skeletal muscle but a role for IL-18 in muscle has not been identified. Patients with HIV-infection and lipodystrophy (LD) are characterized by lipid and glucose disturbances and increased levels of circulating IL-18. We hypothesized that skeletal muscle IL-18 and IL-18 receptor (R) expression would be altered in patients with HIV-lipodystrophy.Twenty-three HIV-infected patients with LD and 15 age-matched healthy controls were included in a cross-sectional study. Biopsies from the vastus lateralis muscle were obtained and IL-18 and IL-18R mRNA expression were measured by real-time PCR and sphingolipids (ceramides, sphingosine, sphingosine-1-Phosphate, sphinganine) were measured by HPLC. Insulin resistance was assessed by HOMA and the insulin response during an OGTT.Patients with HIV-LD had a 60% and 54% lower level of muscular IL-18 and IL-18R mRNA expression, respectively, compared to age-matched healthy controls. Patients with HIV-LD had a trend towards increased levels of ceramide (18.3±4.7 versus 14.8±3.0,p = 0.06) and sphingosine (0.41±0.13 versus 0.32±0.07, and lower level of sphinganine (p = 0.06). Low levels of muscle IL-18 mRNA correlated to high levels of ceramides (r = -0.31, p = 0.038) and sphingosine-1P (r = -0.29, p = 0.046) in skeletal muscle, whereas such a correlation was not found in healthy controls. Low expression of IL-18 mRNA in skeletal muscle correlated to elevated concentration of circulating triglycerides (Rp = -0.73, p<0.0001). Neither muscle expression of IL-18 mRNA or ceramide correlated to parameters of insulin resistance.IL-18 (mRNA) in skeletal muscle appears to be involved in the regulation of intramuscular lipid metabolism and hypertriglyceridemia

Characteristics Associated with Serological Covid-19 Vaccine Response and Durability in an Older Population with Significant Comorbidity:The Danish Nationwide ENFORCE Study

OBJECTIVES: To identify individual characteristics associated with serological COVID-19 vaccine responsiveness and durability of vaccine-induced antibodies. METHODS: Adults without history of SARS-CoV-2 infection from the Danish population scheduled for SARS-CoV-2 vaccination were enrolled in this parallel group, phase IV study. SARS-CoV-2 Spike IgG and Spike-ACE2-receptor-blocking antibodies were measured at days 0, 21, 90 and 180. Vaccine responsiveness was categorized according to Spike IgG and Spike-ACE2-receptor-blocking levels at day 90 post-1(st) vaccination. Non-durable vaccine-response was defined as day 90 responders that no longer had significant responses by day 180. RESULTS: Of 6544 participants completing two vaccine doses (median age 64, interquartile range:54–75), 3654 (55.8%) received BTN162b2, 2472 (37.8%) mRNA-1273, and 418 (6.4%) ChAdOx1 followed by a mRNA vaccine. Levels of both types of antibodies increased from baseline to day 90 and then decreased to day 180. The decrease was more pronounced for levels of Spike-ACE2-receptor-blocking antibodies than for Spike IgG. Proportions with vaccine hypo-responsiveness and lack of durable response were 5.0% and 12.1% for Spike IgG; 12.7% and 39.6% for Spike-ACE2-receptor-blocking antibody levels, respectively. Male sex, vaccine type and number of co-morbidities were associated with all four outcomes. Additionally, age >=75y was associated with hypo-responsiveness for Spike-ACE2-receptor-blocking antibodies (adjusted odds-ratio:1.59, 95% confidence interval:1.25–2.01) but not for Spike IgG. CONCLUSIONS: Comorbidity, male sex and vaccine type were risk factors for hypo-responsiveness and non-durable response to COVID-19 vaccination. The functional activity of vaccine-induced antibodies declined with increasing age and had waned to pre-2(nd) vaccination levels for most individuals after 6 months

Nordisk Konkurrencekraft : – barrierer for erhvervsmæssig synergi

Mange nordiske virksomheder er i gang med en stor omstilling til en global markedssituation, hvor der handles, købes og samarbejdes over hele verden. Det er sket gennem de sidste 10-15 år, hvor import og eksportandele til det globale marked er vokset kraftigt for de fem nordiske lande. Men Norden er stadig et centralt omdrejningspunkt for handel, alliancer og for udveksling af viden. Det viser analysen af de nordiske landes handel internt i Norden og med omverdenen, ligesom det fremgår af virksomhedernes nordiske strategier. Behovet for at skabe gode rammebetingelser for de nordiske virksomheder er derfor fortsat stort. Men arbejdet med at fjerne grænsehindringer er nu så godt i gang og har nået så fine resultater, at næste skridt i den nordiske erhvervsmæssige integration må overvejes. Det er et skridt, hvor de nordiske erhvervsfremmeindsatser, forskningsprogrammer og innovationsprojekter åbnes for nordiske virksomheder, så der dannes et nordisk hjemmemarked for viden. Ved at skabe et stærkt forsknings- og innovationssystem i Norden øges ressourcebasen for de nordiske virksomheder og Norden tyrkes som regionalt vækstcenter. Rapporten giver svar på fem centrale spørgsmål om de erhvervsmæssige perspektiver i en samlet region: Hvor langt er den erhvervsmæssige integration i Norden nået i dag, og hvor konkurrencedygtig er Norden? Hvordan udnytter virksomhederne mulighederne i Norden i dag? Hvilke væsentlige barrierer for at udnytte mulighederne i Norden oplever virksomhederne? Hvilke barrierer og indsatser har særlig betydning for regionens erhvervsmæssige styrkepositioner? Hvilke initiativer kan fremme den erhvervsmæssige integration i Norden