Unmet Physical Activity Need in Old Age

OBJECTIVES: To examine which individual and environmental factors correlate with unmet physical activity need in old age and predict development of unmet physical activity need (the feeling that one's level of physical activity is inadequate and thus distinct from the recommended amount of physical activity) over a 2‐year follow‐up. DESIGN: Observational prospective cohort study and cross‐sectional analyses. SETTING: Community and research center. PARTICIPANTS: A total of 643 community‐living ambulatory people aged 75 to 81 took part in face‐to‐face interviews and examinations at baseline and 314 at the 2‐year follow‐up. MEASUREMENTS: Unmet physical activity need and its potential individual and environmental correlates were assessed at baseline. Development of unmet physical activity need was assessed over the 2‐year follow‐up period. RESULTS: At baseline, all participants were able to walk at least 500 m outdoors, but 14% perceived unmet physical activity need. Unmet physical activity need was more prevalent in those with musculoskeletal diseases, depressive symptoms, and mobility limitations. Hills in the nearby environment, lack of resting places, and dangerous crossroads correlated with unmet physical activity need at baseline; the association was especially strong in those with walking difficulties. Significant baseline predictors for incident unmet physical activity need (15%) included fear of moving outdoors, hills in the nearby environment, and noisy traffic. CONCLUSION: Unmet physical activity need is common in ambulatory community‐living older people who have health and mobility problems and report negative environmental features in their neighborhood. Solutions to overcome barriers to physical activity need to be developed to promote equal opportunities for physical activity participation.     

Perioperative analgesia strategies in fast-track pediatric surgery of the kidney and renal pelvis: lessons learned

Purpose  

Effective analgesia is essential for the success of fast-track (FT) pediatric surgery. Aim of the study was to achieve an optimal analgesia protocol for a comfortable postoperative course and early mobilization in children undergoing urological procedures.     

Age and obesity-associated changes in the expression and activation of components of the AMPK signaling pathway in human right atrial tissue

Background

Obesity is associated with an increased incidence of left ventricular hypertrophy, diastolic dysfunction, heart failure, and premature cardiac aging. In the heart, intrinsic activation of the AMP-dependent protein kinase (AMPK) plays a pivotal role in the stress response to ischemia and hypertrophy. Furthermore, AMPK is an important regulator of cardiac mitochondrial biogenesis. The purpose of the present study was to investigate the influence of obesity and aging on the AMPK signaling pathway in human cardiac tissue.

Methods

60 male cardiac surgery patients were included in the study and divided into 4 groups (old normal weight: ON; old obese: OO; young normal weight: YN, young obese: YO) according to their body mass index (18.5–25: normal weight or 30–35: obese) and age (< 55 years: young or > 70: old) with 15 patients each. Right atrial tissue (RA) was analyzed for the expression of the AMPK upstream kinases CAMKK and LKB1, activation of AMPK as well as phosphorylation of the AMPK downstream targets ACC, eEF2, mTOR and eNOS. Epicardial adipose tissue was analyzed for the expression of the endogenous AMPK activator adiponectin. The metabolic state of all patients was further characterized in fasting blood samples.

Results

Old patients (ON, OO) and young obese (YO) subjects displayed higher fasting glucose, insulin and leptin serum levels compared to the young, normal weight group, although HbA1c was below the threshold required for the diagnosis of type 2 diabetes. Serum adiponectin as well as total adiponectin protein expression in epicardial adipose tissue was decreased in these three groups. Analyses of adiponectin isoforms by native gel electrophoresis revealed significant differences in the high molecular weight (HMW) isoforms between the groups. Despite the low total serum adiponectin and HMW adiponectin, AMPK activation was high in the RA of obese patients (YO, OO). Among the AMPK upstream kinases, LKB1 expression showed a strong positive correlation with AMPK activation. While the phosphorylation of the AMPK downstream targets mTOR, eEF-2 and ACC was not altered, phospho-eNOS was significantly lower in old patients (ON, OO). Despite strong AMPK activation, mitochondrial biogenesis and respiration were impaired in old (ON, OO) and young obese (YO) subjects.

Conclusion

These data indicate that obesity and aging result in significant changes although many direct parameters in the AMPK signaling pathway are not changed in the same direction. LKB1 may represent a stronger activator of the AMPK pathway than adiponectin or the CAMKKs in human right atrial tissue.     

Cell-polymer interactions of fluorescent polystyrene latex particles coated with thermosensitive poly(N-isopropylacrylamide) and poly(N-vinylcaprolactam) or grafted with poly(ethylene oxide)-macromonomer

Cell-polymer interactions of thermosensitive poly(N-isopropylacrylamide) (PNIPAM) or poly(N-vinylcaprolactam) (PVCL) coated particles with RAW264.7 macrophages and intestinal Caco-2 cells were evaluated. Nanosized particles were prepared by modifying the surface of fluorescent polystyrene (FPS) particles with the thermosensitive polymer gels or with poly(ethylene oxide) (PEO)-macromonomer grafts. The particles were characterized by IR-spectroscopy for functional groups, light scattering for size distribution and zeta-potential for surface charge. Effects of temperature and polymer coating/grafting on the cellular interactions were evaluated by cell association/uptake and visualized by confocal scanning microscope. PEO and PNIPAM inhibited the polymer-cell contact by steric repulsion, evidenced by weak attachment of the particles. PVCL-coated FPS was adsorbed on the cells more strongly, especially at 37 degrees C, because of more hydrophobic nature at higher temperatures. The results suggest feasibility of the PNIPAM and PVCL for biotechnological/pharmaceutical applications, as the cell-particle interactions may be modified by size, surface charge, hydrophobicity, steric repulsion and temperature.     

18q deletions: clinical, molecular, and brain MRI findings of 14 individuals

We studied 14 individuals with partial deletions of the long arm of chromosome 18, including terminal and interstitial de novo and inherited deletions. Study participants were examined clinically and by brain MRI. The size of the deletion was determined by segregation analysis using microsatellite markers. We observed that the phenotype was highly variable, even in two families with three 1st degree relatives. Among the 14 individuals, general intelligence varied from normal to severe mental retardation. The more common features of 18q-deletions (e.g., foot deformities, aural atresia, palatal abnormalities, dysmyelination, and nystagmus) were present in individuals lacking only the distal portion 18q22.3-qtel. Interstitial deletions exerted very heterogeneous effects on phenotype. In individuals with distal 18q22.3-q23 deletions, brain MRI was very distinctive with poor differentiation of gray and white matter on T2-weighted images.     

The Fusarium mycotoxins enniatins and beauvericin cause mitochondrial dysfunction by affecting the mitochondrial volume regulation,oxidative phosphorylation and ion homeostasis

The mechanisms of cell toxicity of mycotoxins of the enniatin family produced by Fusarium sp. enniatin B, a mixture of enniatin homologues (3% A, 20% A₁, 19% B, 54% B1) and beauvericin, were investigated. In isolated rat liver mitochondria, exposure to submicromolar concentrations of the enniatin mycotoxins depleted the mitochondrial transmembrane potential, uncoupled oxidative phosphorylation, induced mitochondrial swelling and decreased calcium retention capacity of the mitochondria. The mitochondrial effects were strongly connected with the potassium (K⁺) ionophoric activity of the enniatins. The observed enniatins induced K⁺ uptake by mitochondria. This shows that the enniatins acted as ionophores highly selective for potassium ions. The effects were observed in potassium containing media whereas less or no effect remained to be observed when K⁺ was partially or totally replaced by isomolar concentrations of Na⁺. The rank order of enniatin induced mitochondrial impairment was beauvericin > enniatin mixture > enniatin B. Exposure to the enniatins depleted the mitochondrial membrane potential also in intact human neural (Paju), murine insulinoma (Min-6) cells as well as boar spermatozoa. Exposure to enniatin B in media with physiological (4 mM) or low (<1 mM) but not in high (60 mM) external concentration of K⁺ induced hyperpolarization of the spermatozoal plasma membrane indicating enniatin that catalysed efflux of the cytosolic K⁺ ions. These results indicate that the cellular toxicity targets of the enniatin mycotoxins are the mitochondrion and the homeostasis of potassium ions.     

Prostate Cancer Mortality Reduction by Prostate-Specific Antigen–Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)

Background

Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm.

Objective

To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination.

Design, setting, and participants

We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55–69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent).

Intervention

Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam.

Measurements

Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose.

Results and limitations

In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68–0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58–0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51–0.92) to 0.71 (95% CI, 0.55–0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres.

Conclusions

PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.     

Regional myocardial perfusion abnormalities: Fractional flow reserve versus cardiac magnetic resonance first-pass perfusion imaging

Identification of the functional severity of intermediate coronary artery lesions is challenging for the interventional cardiologist. Functional severity can be measured invasively using the fractional flow reserve (FFR). However, FFR has the disadvantage of being invasive and associated with radiation exposure. Cardiac MRI (CMR) offers the opportunity to assess myocardial perfusion noninvasively. A semiquantitative index of myocardial perfusion (perfusion reserve index or PRI) can be obtained from the first-pass of a bolus of gadolinium through the myocardium. Studies comparing the invasive FFR to CMR perfusion imaging in patients with coronary artery stenosis of undefined significance have demonstrated that CMR first-pass perfusion imaging may be useful for the assessment of their functional significance. However, in patients with a high prevalence of microvascular dysfunction, the value of this method may be limited because the PRI may be influenced by both the epicardial conductance vessel function as well as microvascular function.     

Unexpected hemodynamic depression after induction of anaesthesia

Patients with coronary artery disease (CAD) undergoing noncardiac surgery (NCS) pose a special challenge for the anaesthesiologist, as the risk of serious perioperative cardiac complications, which represent a significant cause of morbidity and mortality, is increased in this population. Here we report about a patient with a solitary liver metastasis, who was admitted for hemihepatectomy. The patient with a known single vessel CAD, reporting no current cardiac problems, was cleared for the surgical procedure which carries a high risk of cardiac complications. Cardiology reports were present for evaluation. After an unremarkable placement of the peridural catheter and endotracheal intubation the patient presented with bradycardia and hypotension. Pharmacological resuscitation was initiated. After the patient was stabilized and the differential diagnosis suggested a cardiac problem, surgery was postponed. Following the end of anaesthesia, the patient remained in stable condition without catecholamine support. Coronary angiography on the next day revealed a progression of the CAD. The peridural catheter was removed before the intervention, Aspirin and clopidogrel were given on the same day. The patient was operated successfully without complications six weeks after the coronary intervention.