AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan

Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. Metabolic syndrome is associated with a low-grade, chronic inflammation, primarily in adipose tissue. A low-level of inflammation is also present in the aging process. There are emerging results indicating that AMPK signaling can inhibit the inflammatory responses induced by the nuclear factor-κB (NF-κB) system. The NF-κB subunits are not direct phosphorylation targets of AMPK, but the inhibition of NF-κB signaling is mediated by several downstream targets of AMPK, e.g., SIRT1, PGC-1α, p53, and Forkhead box O (FoxO) factors. AMPK signaling seems to enhance energy metabolism while it can repress inflammatory responses linked to chronic stress, e.g., in nutritional overload and during the aging process. AMPK can inhibit endoplasmic reticulum and oxidative stresses which are involved in metabolic disorders and the aging process. Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. The activation capacity of AMPK declines in metabolic stress and with aging which could augment the metabolic diseases and accelerate the aging process. We will review the AMPK pathways involved in the inhibition of NF-κB signaling and suppression of inflammation. We also emphasize that the capacity of AMPK to repress inflammatory responses can have a significant impact on both healthspan and lifespan

Attitudes Regarding Occupational Vaccines and Vaccination Coverage Against Vaccine-preventable Diseases Among Healthcare Workers Working in Pediatric Departments in Greece

We studied the attitudes with regard to occupational vaccines and vaccination coverage among healthcare workers in pediatric departments. Completed vaccination rates were 33%, 33%, 41.7%, 3%, 5.8%, 69.2% and 36.3% against measles, mumps, rubella, varicella, hepatitis A, hepatitis B and tetanus-diphtheria, respectively. Susceptibility rates were 14.2%, 15.7%, 14.6%, 7.6%, 87.4%, 22.6% and 61.8% for measles, mumps, rubella, varicella, hepatitis A, hepatitis B and tetanus-diphtheria, respectively. Mandatory vaccinations were supported by 70.6% of healthcare workers, with considerable differences by target disease

Expression of NEDD4L and ENaC in Urinary Extracellular Vesicles in Pre-eclampsia

Objective To assess changes in expression of renal epithelial sodium channel (ENaC) and NEDD4L, a ubiquitin ligase, in urinary extracellular vesicles (UEV) of pre-eclamptic women compared to normal pregnant controls. Methods Urine was collected from pre-eclamptic women (PE, n = 20) or during normal pregnancy (NP, n = 20). UEV were separated by differential ultracentrifugation. NEDD4L, α-ENaC and γ-ENaC were identified by immunoblotting. Results There was no difference in the expression of NEDD4L (p = 0.17) and α-ENaC (p = 0.10). PE subjects showed increased expression of γ-ENaC by 6.9-fold compared to NP (p < 0.0001). Conclusion ENaC expression is upregulated in UEV of pre-eclamptic subjects but was not associated with changes in NEDD4L

Impact of postpartum influenza vaccination of mothers and household contacts in preventing febrile episodes, influenza-like illness, healthcare seeking, and administration of antibiotics in young infants during the 2012-2013 influenza season

Background. Influenza is associated with an increased risk for serious illness, hospitalization, and mortality in infants aged &lt;6 months. However, influenza vaccines are not licensed for administration in this age group. The study evaluated the effectiveness of postpartum influenza vaccination of mothers and household members in infants. Methods. The influenza vaccine was offered to mothers and household members of neonates born or hospitalized in 3 hospitals prior to the 2012-2013 season. Mothers were contacted every 2 weeks during the influenza season, and data regarding the onset of fever and/or respiratory symptoms in infants, healthcare seeking, hospitalization, and administration of antibiotics were collected. Results. The study group consisted of 553 mothers who delivered 573 neonates. The influenza vaccine was administered to 841 of 1844 (45.6%) household contacts. Vaccination coverage rates ranged between 41.9% for neonates siblings and 49% for mothers. Five hundred thirty infants were analyzed for vaccine effectiveness. For outcomes in the infant, postpartum maternal vaccination had 37.7% effectiveness against acute respiratory illness (ARI), 50.3% against a febrile episode, 53.5% against influenza-like illness (ILI), 41.8% against related healthcare seeking, and 45.4% against administration of antibiotics. Multiple logistic regression analyses showed that maternal influenza vaccination was significantly associated with a decreased probability for febrile episodes, ARIs, and/or ILIs in infants, related healthcare seeking, and/or administration of antibiotics during the influenza season. Vaccination of other household contacts had no impact. Conclusions. Maternal postpartum vaccination against influenza was associated with a significant reduction of influenza-related morbidity, healthcare seeking, and antibiotic prescription in infants during the influenza season. © The Author 2013

Acceptance of a post-partum influenza vaccination (cocooning) strategy for neonates in Greece

Young infants are at increased risk for influenza-associated serious illness, onset of complications, utilization of health-care services, and hospitalization. We investigated the feasibility and acceptance of an influenza vaccination (cocooning) strategy by household contacts implemented in a maternity hospital and the neonatal unit of a pediatric hospital in Athens. A total of 224 mothers (mean age: 30.2 years) who gave birth to 242 neonates were studied. Of them, 165 (73.7%) mothers were vaccinated. Multiple logistic regression revealed that statistically significant factors associated with increased vaccination rates among mothers were: being of Roma origin (p-value = 0.002), being an immigrant (p-value = 0.025), giving birth to a neonate with birth weight &lt;2500. g (p-value = 0.012), and residing in a family with ≥4 family members (p-value = 0.017). Of the 224 fathers, 125 (55.8%) received the influenza vaccine. Fathers of neonates whose mothers were vaccinated had 6-fold higher vaccination rates compared to fathers of neonates whose mothers refused vaccination (p-value &lt; 0.001). Overall, influenza vaccine was administered to 348 (46.9%) of a total of 742 household contacts of the 242 neonates. Upon entering the 2011-2012 influenza season, 51 (22.7%) of 224 families had all household contacts vaccinated against influenza (complete cocoon). Among parents, the statement &quot;I do not want to receive the vaccine&quot; was the prevalent reason for declining influenza vaccination, followed by the misconception &quot;I am not at risk for contacting influenza&quot; (41.1% and 38.2%, respectively). © 2012 Elsevier Ltd

Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia

Abstract Background Glycolysis is altered in various kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the kidney. Urinary exosomes provide a non-invasive alternative for studying changes in kidney metabolism. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia (PE), compared to normotensive non-pregnant (NC) and normotensive pregnant (NP) controls. Methods A cross-sectional study of NC (n = 19), NP (n = 23) and PE (n = 29) subjects was performed. Exosomes were isolated from urine samples by differential ultracentrifugation, and then analyzed by Western blot and densitometry for expression of PFK-2/FBPase-2 isozymes (PFKFB2, PFKFB3 and PFKFB4) and phosphorylation of PFKFB2 at residues Ser483 and Ser466 and PFKFB3 at Ser461. Results PFKFB2 expression was increased 4.7-fold in PE compared to NP (p < 0.001). PFKFB2 phosphorylation at Ser483 was increased 2.6-fold in PE compared to NP (p = 0.002). Expression of phosphorylated PFKFB2/PFKFB3 at Ser466/Ser461 was increased in PE, being present in 77.4% (95% CI 59.9–88.9%) of PE and 8.3% (95% CI 1.2–27.0%) of NP samples (p < 0.001). PFKFB3 was more commonly expressed in PE, detected in 90.3% (95% CI 74.3–97.4%) of PE and 8.3% (95% CI 1.2–27.0%) of NP samples (p < 0.001). PFKFB4 had a 7.2-fold increase in expression in PE compared to NP (p < 0.001). No significant differences between NP and NC groups were observed. Conclusion Regulatory proteins that increase glycolysis are increased in the urinary exosomes of subjects with pre-eclampsia, suggesting that renal glycolysis may be increased in this condition

Pre-eclampsia is associated with altered expression of the renal sodium transporters NKCC2, NCC and ENaC in urinary extracellular vesicles

Pre-eclampsia is a hypertensive disorder of pregnancy characterised by hypertension and sodium retention by the kidneys. To identify changes in sodium uptake proteins in the tubules of the distal nephron, we studied their expression in urinary extracellular vesicles or exosomes (uEVs). Urine was collected from women with pre-eclampsia or during normal pregnancy, and from healthy non-pregnant controls. uEVs were isolated by centrifugation and analyzed by Western blot. Expression, proteolytic cleavage and phosphorylation was determined by densitometric analysis normalized to the exosome marker CD9. Results showed a significant increase in phosphorylation of the activating S130 site in NKCC2, the drug target for frusemide, in women with pre-eclampsia compared with normal pregnant women. Phosphorylation of the activating sites T101/105 in NKCC2 was similar but the activating T60 site in NCC, the drug target for thiazide diuretics, showed significantly less phosphorylation in pre-eclampsia compared with normal pregnancy. Expression of the larger forms of the α subunit of ENaC, the drug target for amiloride, was significantly greater in pre-eclampsia, with more fragmentation of theγ subunit. The differences observed are predicted to increase the activity of NKCC2 and ENaC while reducing that of NCC. This will increase sodium reabsorption, and so contribute to hypertension in pre-eclampsia

Seroepidemiological study of pandemic influenza H1N1 following the 2009-2010 wave in Greece

Knowledge of seroprevalence rates against 2009 pandemic H1N1 virus will assist vaccination recommendations and the preparation of the health-care system during subsequent years. This study was conducted in Greece during June-August 2010 to estimate the seroprevalence rate against pandemic H1N1 virus. Persons presenting in 29 health-care facilities across the country were studied. Seroprevalence was estimated employing a virus-free ELISA that specifically recognizes 2009 H1N1 virus antibodies in human sera. Sera collected from 2005 to April 2009 were also used to estimate pre-pandemic seroprevalence rates. A total of 954 persons were studied. The overall seroprevalence rate was 28.5% (95% confidence interval =25.6-31.3%). Age-specific rates were 34.2% in persons 0-4 years, 36.3% in persons 5-19 years, 25.0% in persons 20-39 years, 23.4% in persons 40-59 years, and 31.8% in persons ≥60 years. The highest rates were recorded in the Regions of Ionian Islands (67%) and Epirus (42.9%), while the lowest (8.4%) in the Region of Thessaly. Age-specific attack rates of infection during 2009-2010 were 28.8% in persons 0-4 years, 32.5% in persons 5-19 years, 14.3% in persons 20-39 years, 19.1% in persons 40-59 years, and 14.4% in persons ≥60 years. Multivariate analysis revealed that Region of residence and caring for children &lt;5 years were associated with increased risk for seropositivity. Urbanity, personal and family characteristics, working in a health-care facility or in a school, history of pandemic H1N1 vaccination or history of influenza-like illness during 2009-2010 were not associated with increased risk for seropositivity. © 2011 Elsevier Ltd