ICU-acquired muscle weakness commonly occurs in patients with septic shock and is associated with poor outcome. Although atrophy is known to be involved, it is unclear whether ligands in plasma from ...these patients are responsible for initiating degradation of muscle proteins. The aim of the present study was to investigate if plasma from septic shock patients induces skeletal muscle atrophy and to examine the time course of plasma-induced muscle atrophy during ICU stay.
Plasma was derived from septic shock patients within 24 hours after hospital admission (n = 21) and healthy controls (n = 12). From nine patients with septic shock plasma was additionally derived at two, five and seven days after ICU admission. These plasma samples were added to skeletal myotubes, cultured from murine myoblasts. After incubation for 24 hours, myotubes were harvested and analyzed on myosin content, mRNA expression of E3-ligase and Nuclear Factor Kappa B (NFκB) activity. Plasma samples were analyzed on cytokine concentrations.
Myosin content was approximately 25% lower in myotubes exposed to plasma from septic shock patients than in myotubes exposed to plasma from controls (P < 0.01). Furthermore, patient plasma increased expression of E3-ligases Muscle RING Finger protein-1 (MuRF-1) and Muscle Atrophy F-box protein (MAFbx) (P < 0.01), enhanced NFκB activity (P < 0.05) and elevated levels of ubiquitinated myosin in myotubes. Myosin loss was significantly associated with elevated plasma levels of interleukin (IL)-6 in septic shock patients (P < 0.001). Addition of antiIL-6 to septic shock plasma diminished the loss of myosin in exposed myotubes by approximately 25% (P < 0.05). Patient plasma obtained later during ICU stay did not significantly reduce myosin content compared to controls.
Plasma from patients with septic shock induces loss of myosin and activates key regulators of proteolysis in skeletal myotubes. IL-6 is an important player in sepsis-induced muscle atrophy in this model. The potential to induce atrophy is strongest in plasma obtained during the early phase of human sepsis.
Main text We greatly appreciate the efforts made by Sievi and colleagues to verify our recent findings about the ‘can do, do do’ concept for patients with COPD and expand our understanding on the ...long-term dynamics of the quadrant affiliation 1, 2. Since a personalized intervention to improve physical functioning for a patient with COPD may be derived from the quadrant affiliations, interventions should be congruent with the actual ‘can do, do do’ status. ...a further analysis on all these aspects is required to customize an appropriate intervention for patients in the ‘can do, don’t do’ quadrant. ...would changes in quadrant allocation over time occur, then it does not in any way diminish the applicability of the ‘can do, do do’ concept to provide customized care to improve physical functioning.
Large epidemiological studies that use accelerometers for physical behavior and sleep assessment differ in the location of the accelerometer attachment and the signal aggregation metric chosen. This ...study aimed to assess the comparability of acceleration metrics between commonly-used body-attachment locations for 24 hours, waking and sleeping hours, and to test comparability of PA cut points between dominant and non-dominant wrist. Forty-five young adults (23 women, 18-41 years) were included and GT3X + accelerometers (ActiGraph, Pensacola, FL, USA) were placed on their right hip, dominant, and non-dominant wrist for 7 days. We derived Euclidean Norm Minus One g (ENMO), Low-pass filtered ENMO (LFENMO), Mean Amplitude Deviation (MAD) and ActiGraph activity counts over 5-second epochs from the raw accelerations. Metric values were compared using a correlation analysis, and by plotting the differences by time of the day. Cut points for the dominant wrist were derived using Lin's concordance correlation coefficient optimization in a grid of possible thresholds, using the non-dominant wrist estimates as reference. They were cross-validated in a separate sample (N = 36, 10 women, 22-30 years). Shared variances between pairs of acceleration metrics varied across sites and metric pairs (range in r
: 0.19-0.97, all p < 0.01), suggesting that some sites and metrics are associated, and others are not. We observed higher metric values in dominant vs. non-dominant wrist, thus, we developed cut points for dominant wrist based on ENMO to classify sedentary time (<50 mg), light PA (50-110 mg), moderate PA (110-440 mg) and vigorous PA (≥440 mg). Our findings suggest differences between dominant and non-dominant wrist, and we proposed new cut points to attenuate these differences. ENMO and LFENMO were the most similar metrics, and they showed good comparability with MAD. However, counts were not comparable with ENMO, LFENMO and MAD.
The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency and increases morbidity, duration of hospital stay, and health care costs. The ...mechanisms underlying diaphragm weakness are unknown, but might include mitochondrial dysfunction and oxidative stress.
We hypothesized that weakness of diaphragm muscle fibers in critically ill patients is accompanied by impaired mitochondrial function and structure, and by increased markers of oxidative stress.
To test these hypotheses, we studied contractile force, mitochondrial function, and mitochondrial structure in diaphragm muscle fibers. Fibers were isolated from diaphragm biopsies of 36 mechanically ventilated critically ill patients and compared with those isolated from biopsies of 27 patients with suspected early-stage lung malignancy (control subjects).
Diaphragm muscle fibers from critically ill patients displayed significant atrophy and contractile weakness, but lacked impaired mitochondrial respiration and increased levels of oxidative stress markers. Mitochondrial energy status and morphology were not altered, despite a lower content of fusion proteins.
Critically ill patients have manifest diaphragm muscle fiber atrophy and weakness in the absence of mitochondrial dysfunction and oxidative stress. Thus, mitochondrial dysfunction and oxidative stress do not play a causative role in the development of atrophy and contractile weakness of the diaphragm in critically ill patients.
Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly ...understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being.
•Latent Class Analysis (LCA), a person-oriented statistical analysis, was used.•LCA found four patterns of social participation in older adults with disabilities.•Patterns in social networks differ ...from patterns of social informal activities.•The level of social participation is related to individual factors and well-being.•A social participation typology may help to assess the risk for reduced well-being.
Living with a chronic condition or a disability at older age impacts social participation. Social connections and social activities seem interrelated leading to heterogeneous patterns in social participation. The aim of this study was to identify a typology in social participation among older adults with disabilities, and to relate this typology to their background characteristics and well-being measures.
A total of 1775 older adults with disabilities or chronic conditions aged 65–97 were sampled from a nationwide panel study in the Netherlands. Social participation was assessed by various measures related to social connections, social informal activities, voluntary work, effort to increase social participation, and online social participation. A latent class analysis was carried out to identify a typology of social participation. Differences between these classes were explored with multinomial regression analyses and pairwise comparisons.
Four classes were found: social withdrawers (22.5%, n = 399), proximate social dwellers (14.5%, n = 257), moderately active social dwellers (37.2%, n = 660) and pro-active social dwellers (25.9%, n = 459). Background characteristics, such as living alone and severity of disability, differed significantly among classes. Regarding well-being measures, it appeared that pro-active social dwellers had the most positive scores. Social withdrawers were most prone to reduced life satisfaction and health related quality of life and increased loneliness and experienced participation restrictions.
A typology with four patterns based on a wide spectrum of social participation aspects in older adults with disabilities was identified. This typology may help to assess the risk for reduced well-being of older adults with disabilities.
Weaning of piglets causes stress due to environmental, behavioral, and nutritional stressors and can lead to postweaning diarrhea and impaired gut development. The diet changes experienced during ...weaning require extensive adaptation of the digestive system. A well-developed piglet that had creep-feed experience before weaning performs better after weaning. In the current study, the effect of providing sow-fed piglets with a supplemental nutrient-dense complex milk replacer (NDM) on gut development and growth performance was studied. Litters of sows with similar parities (3.6 ± 0.8) and similar numbers of live born piglets (13.5 ± 0.3) were assigned to 1 of 2 groups: 1 group of piglets had ad libitum access to NDM from Day 2 through 21 after birth, whereas the other group was used as controls. Nutrient-dense complex milk replacer-fed piglets were shown to be significantly heavier after 21 d of supplementation compared with the control piglets. At Day 21, 3 piglets from each litter were euthanized for morphological and functional analyses of the intestinal tract. The small intestines of NDM-fed piglets had significantly higher weights (g) as well as significantly higher relative weight:length ratios (g//cm) compared with the small intestines of control piglets ( < 0.05). Morphometric analysis demonstrated that villi length and numbers of goblet cells did not differ between groups. However, NDM-fed piglets had deeper crypts ( < 0.001) and an increased expression of the cell-proliferation marker proliferating cell nuclear antigen in crypts ( < 0.05), suggesting higher cell-proliferation rates. The gene encoding IGF-1 showed a tendency to higher gene expression in the jejunum from NDM-fed piglets ( = 0.07) compared with the jejunum from control piglets, suggesting that IGF-1 might be involved in the regulation of cell proliferation and intestinal growth. Finally, as a result of dietary fiber in NDM, piglets showed significantly increased concentrations of metabolic fermentation products. This suggests differences in metabolic activity in the colon between treatment groups. In conclusion, providing sow-fed piglets with NDM before weaning stimulates intestinal proliferation, leading to increased circular growth. Nutrient-dense complex milk replacer supplementation might, therefore, help piglets through the transition period at weaning by increased BW and increased capacity for uptake of nutrients.
Studies on the systemic availability of nutrients and nutritional status in Alzheimer's disease (AD) are widely available, but the majority included patients in a moderate stage of AD.
This study ...compares the nutritional status between mild AD outpatients and healthy controls.
A subgroup of Dutch drug-naïve patients with mild AD (Mini-Mental State Examination (MMSE) ≥20) from the Souvenir II randomized controlled study (NTR1975) and a group of Dutch healthy controls were included. Nutritional status was assessed by measuring levels of several nutrients, conducting the Mini Nutritional Assessment (MNA®) questionnaire and through anthropometric measures.
In total, data of 93 healthy cognitively intact controls (MMSE 29.0 23.0-30.0) and 79 very mild AD patients (MMSE = 25.0 20.0-30.0) were included. Plasma selenium (p < 0.001) and uridine (p = 0.046) levels were significantly lower in AD patients, with a similar trend for plasma vitamin D (p = 0.094) levels. In addition, the fatty acid profile in erythrocyte membranes was different between groups for several fatty acids. Mean MNA screening score was significantly lower in AD patients (p = 0.008), but not indicative of malnutrition risk. No significant differences were observed for other micronutrient or anthropometric parameters.
In non-malnourished patients with very mild AD, lower levels of some micronutrients, a different fatty acid profile in erythrocyte membranes and a slightly but significantly lower MNA screening score were observed. This suggests that subtle differences in nutrient status are present already in a very early stage of AD and in the absence of protein/energy malnutrition.
•Plasma bicarbonate increased in healthy subjects by ingesting sodium bicarbonate.•With increasing inspiratory CO2 pressure, breathing parameters increased.•The ratio ΔVE/ΔPetCO2 remained unchanged ...with increased plasma bicarbonate.•Respiratory drive and minute ventilation decreased with increased plasma bicarbonate.
Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma bicarbonate levels decrease respiratory drive and minute ventilation.
In an intervention study in 10 healthy subjects the ventilatory response using a hypercapnic ventilatory response (HCVR) test was assessed, before and after administration of high dose sodium bicarbonate. Total dose of sodiumbicarbonate was 1000 ml 8.4% in 3 days.
Plasma bicarbonate increased from 25.2 ± 2.2 to 29.2 ± 1.9 mmol/L. With increasing inspiratory CO2 pressure during the HCVR test, RR, Vt, Pdi, EAdi and VE increased. The clinical ratio ΔVE/ΔPetCO2 remained unchanged, but Pdi, EAdi and VE were significantly lower after bicarbonate administration for similar levels of inspired CO2.
This study demonstrates that in healthy subjects metabolic alkalosis decreases the neural respiratory drive and minute ventilation, as a response to inspiratory CO2.
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