Mitochondrial reactive oxygen species (ROS) production and detoxification are tightly balanced. Shifting this balance enables ROS to activate intracellular signaling and/or induce cellular damage and ...cell death. Increased mitochondrial ROS production is observed in a number of pathological conditions characterized by mitochondrial dysfunction. One important hallmark of these diseases is enhanced glycolytic activity and low or impaired oxidative phosphorylation. This suggests that ROS is involved in glycolysis (dys)regulation and vice versa. Here we focus on the bidirectional link between ROS and the regulation of glucose metabolism. To this end, we provide a basic introduction into mitochondrial energy metabolism, ROS generation and redox homeostasis. Next, we discuss the interactions between cellular glucose metabolism and ROS. ROS-stimulated cellular glucose uptake can stimulate both ROS production and scavenging. When glucose-stimulated ROS production, leading to further glucose uptake, is not adequately counterbalanced by (glucose-stimulated) ROS scavenging systems, a toxic cycle is triggered, ultimately leading to cell death. Here we inventoried the various cellular regulatory mechanisms and negative feedback loops that prevent this cycle from occurring. It is concluded that more insight in these processes is required to understand why they are (un)able to prevent excessive ROS production during various pathological conditions in humans.
Monogenic mitochondrial disorders Koopman, Werner J H; Willems, Peter H G M; Smeitink, Jan A M
The New England journal of medicine,
03/2012, Letnik:
366, Številka:
12
Journal Article
Spin is a fundamental property of all elementary particles. Classically it can be viewed as a tiny magnetic moment, but a measurement of an electron spin along the direction of an external magnetic ...field can have only two outcomes: parallel or anti-parallel to the field. This discreteness reflects the quantum mechanical nature of spin. Ensembles of many spins have found diverse applications ranging from magnetic resonance imaging to magneto-electronic devices, while individual spins are considered as carriers for quantum information. Read-out of single spin states has been achieved using optical techniques, and is within reach of magnetic resonance force microscopy. However, electrical read-out of single spins has so far remained elusive. Here we demonstrate electrical single-shot measurement of the state of an individual electron spin in a semiconductor quantum dot. We use spin-to-charge conversion of a single electron confined in the dot, and detect the single-electron charge using a quantum point contact; the spin measurement visibility is ∼65%. Furthermore, we observe very long single-spin energy relaxation times (up to ∼0.85 ms at a magnetic field of 8 T), which are encouraging for the use of electron spins as carriers of quantum information.
Background
Colorectal cancer is one of the most common cancers worldwide. Laparoscopic colorectal surgery (LCRS) is a frequently used modality. A new development in minimally invasive surgery is ...robot-assisted colorectal surgery (RACRS).
Methods
Prospectively collected data of 378 consecutive patients who underwent RACRS or LCRS for stage I–III colorectal cancer from Dec 2014 to Oct 2017 were analyzed. Primary outcome was oncological outcome (radical margins, number of retrieved lymph nodes, locoregional recurrence). Secondary outcomes were distant metastases, overall and disease-free survival, operation time, conversion, length of hospital stay, and intra- and post-operative complications.
Results
206 RACRS (129 colon and 77 rectal) and 172 LCRS (138 colon and 34 rectal) procedures were included. Baseline characteristics were similar. Overall median follow-up time was 15 months (0.2–36). Oncological outcome was similar. In colon cancer, radical margins were achieved in 99.3% in RACRS group versus 98.6% in LCRS group (
p
= 0.60), the average number of harvested lymph nodes was 16 ± 6 versus 18 ± 7 (
p
= 0.16), and locoregional recurrence rate in 24 months was 3.8% vs 3.8% (
p
= 0.99), respectively. In rectal cancer, radical margins were achieved in 89.6% in RACRS group versus 94.3% in LCRS group (
p
= 0.42), the average number of harvested lymph nodes was 16 ± 8 versus 15 ± 4 (
p
= 0.51), and locoregional recurrence rate in 24 months was 9.5 versus 5.6% (
p
= 0.42), respectively. Incidence of metastasis, survival rates, operation time, length of hospital stay, and number of severe post-operative complications measured by Clavien–Dindo scores did not differ between RACRS and LCRS groups. Conversion and intra-operative complication rates were significantly lower in the RACRS group as compared to the LCRS group (3% vs 9%,
p
= 0.008 and 2% vs 8%,
p
= 0.003, respectively).
Conclusion
RACRS is safe in the treatment of patients with stage I–III colorectal cancer. Oncological outcome did not differ between RACRS and LCRS groups. RACRS had lower conversion and intra-operative complication rates.
Colostrum oligosaccharides are known to exhibit prebiotic and immunomodulatory properties. Oligosaccharide composition is species-specific, and equine colostrum has been reported to contain unique ...oligosaccharides. Therefore, equine oligosaccharides (EMOS) from colostrum from different horse breeds were analyzed by CE-LIF, CE-MS(n), HILIC-MS(n), and exoglycosidase degradation. Sixteen EMOS were characterized and quantified, of which half were neutral and half were acidic. EMOS showed about 63% structural overlap with human milk oligosaccharides, known for their bioactivity. Seven EMOS were not reported before in equine oligosaccharides literature: neutral Gal(β1-4)HexNAc, Gal(β1-4)Hex-Hex, β4'-galactosyllactose, and lactose-N-hexaose, as well as acidic 6'-Sialyl-Hex-Ac-HexNAc, sialyllacto-N-tetraose-a, and disialylacto-N-tetraose (isomer not further specified). In all colostrum samples, the average oligosaccharide concentration ranged from 2.12 to 4.63 g/L; with β 6'and 3'- galactosyllactose, 3'-sialyllactose, and disialyllactose as the most abundant of all oligosaccharides (27-59, 16-37, 1-8, and 1-6%, respectively). Differences in presence and in abundance of specific EMOS were evident not only between the four breeds but also within the breed.
Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. However, it is not well ...established how great the risk is for falls and fractures for the different stages of CKD compared to the general population. The objective of this systematic review and meta-analysis was to assess whether, and in which degree, CKD was associated with falls and fractures in adults. A systematic search in PubMed, Embase, CINAHL, and The Cochrane Library was performed on 7 September 2018. All retrospective, cross-sectional, and longitudinal studies of adults (18 years of older) that studied the association between CKD, fractures, and falls were included. Additional studies were identified by cross-referencing. A total of 39 publications were included, of which two publications assessed three types of outcome and four publications assessed two types of outcome. Ten studies focused on accidental falling; seventeen studies focused on hip, femur, and pelvis fractures; seven studies focused on vertebral fractures; and thirteen studies focused on any type of fracture without further specification. Generally, the risk of fractures increased when kidney function worsened, with the highest risks in the patients with stage 5 CKD or dialysis. This effect was most pronounced for hip fractures and any type of fractures. Furthermore, results on the association between CKD and accidental falling were contradictory. Compared to the general population, fractures are highly prevalent in patients with CKD. Besides more awareness of timely fracture risk assessment, there also should be more focus on fall prevention.
Purpose
The direct effects of galacto-oligosaccharides (GOS), including Vivinal
®
GOS syrup (VGOS) and purified Vivinal
®
GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 ...(IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To investigate structure–activity relationships, the effects of individual DP fractions of VGOS were evaluated. Moreover, the obtained results with GOS were compared with Caco-2 monolayers incubated with fructo-oligosaccharides (FOS) and inulin.
Methods
Caco-2 monolayers were pretreated (24 h) with or without specific oligosaccharides or DP fractions of VGOS (DP2 to DP6) before being exposed for 12 or 24 h to the fungal toxin deoxynivalenol (DON). Transepithelial electrical resistance and lucifer yellow permeability were measured to investigate barrier integrity. A calcium switch assay was used to study the reassembly of tight junction proteins. Release of CXCL8, a typical marker for inflammation, was quantified by ELISA.
Results
In comparison with PGOS, FOS and inulin, VGOS showed the most pronounced protective effect on the DON-induced impairment of the monolayer integrity, acceleration of the tight junction reassembly and the subsequent CXCL8 release. DP2 and DP3 in concentrations occurring in VGOS prevented the DON-induced epithelial barrier disruption, which could be related to their high prevalence in VGOS. However, no effects of the separate DP GOS fractions were observed on CXCL8 release.
Conclusions
This comparative study demonstrates the direct, microbiota-independent effects of oligosaccharides on the intestinal barrier function and shows the differences between individual galacto- and fructo-oligosaccharides. This microbiota-independent effect of oligosaccharides depends on the oligosaccharide structure, DP length and concentration.
Objective
There are marked mitochondrial abnormalities in parkin‐knock‐out Drosophila and other model systems. The aim of our study was to determine mitochondrial function and morphology in ...parkin‐mutant patients. We also investigated whether pharmacological rescue of impaired mitochondrial function may be possible in parkin‐mutant human tissue.
Methods
We used three sets of techniques, namely, biochemical measurements of mitochondrial function, quantitative morphology, and live cell imaging of functional connectivity to assess the mitochondrial respiratory chain, the outer shape and connectivity of the mitochondria, and their functional inner connectivity in fibroblasts from patients with homozygous or compound heterozygous parkin mutations.
Results
Parkin‐mutant cells had lower mitochondrial complex I activity and complex I–linked adenosine triphosphate production, which correlated with a greater degree of mitochondrial branching, suggesting that the functional and morphological effects of parkin are related. Knockdown of parkin in control fibroblasts confirmed that parkin deficiency is sufficient to explain these mitochondrial effects. In contrast, 50% knockdown of parkin, mimicking haploinsufficiency in human patient tissue, did not result in impaired mitochondrial function or morphology. Fluorescence recovery after photobleaching assays demonstrated a lower level of functional connectivity of the mitochondrial matrix, which further worsened after rotenone exposure. Treatment with experimental neuroprotective compounds resulted in a rescue of the mitochondrial membrane potential.
Interpretation
Our study demonstrates marked abnormalities of mitochondrial function and morphology in parkin‐mutant patients and provides proof‐of‐principle data for the potential usefulness of this new model system as a tool to screen for disease‐modifying compounds in genetically homogenous parkinsonian disorders. Ann Neurol 2008;64:555–565
Antlers are formed anew each year to realise an optimal relationship between their size and weight and the physical body condition in
Cervidae
. This results in the objective to match fighting ...abilities with size and mechanical performance of the antlers, as well as to advertise these correlated abilities to other males and females. The resulting variation in individual antler characteristics from year to year can show considerable differences. To characterise and understand these differences is important in hunting, game management and deer breeding, as well as potentially to assess the habitat quality. However, relatively few traits of the antler have been scientifically tested for this purpose, and only a few studies were conducted on the same individual in free-ranging red deer over the years. The objective of the present study was to quantify the influence of the individual (repeatability), the age and the site on the expression of 125 antler characteristics. For this purpose, we collected 35 stags with an average of about 10 consecutive antlers per individual (confirmed by genetic analysis), a total of 355 antlers. The antlers were scanned 3-dimensionally and measured semi-automatically. Numbers, lengths, distances, circumferences, bending, curvatures, angles, forms and CIC (International Council for Game and Wildlife Conservation) characteristics were compiled and evaluated in a generalised linear mixed model adapted to the distribution of the characteristics. The complete model explained 1.6 to 83% of character variation. Mean repeatability of the characteristics varied between 2.7 and 74.4%. The stags’ age explained 0 to 36.4%, and the side explained 0 to 2.5% of the variability. Some characteristics of burr, signet, beam and the lower tines reached the highest repeatability; the highest variability was found in characteristics of the crown. Values of 11 features that are frequently used in other studies corresponded very well with the present study. However, some features reached higher repeatability every year, whereas others varied more closely with age. Such characteristics might be selectively included into further research or practical applications to increase informative value.
Summary
Impaired physical performance is associated with increased fracture risk. Performance on four physical functioning tests and prevalence of sarcopenia were assessed for 1789 fracture patients ...and compared to reference data. Performance was low on all tests, especially for patients with a hip, major or ≥ 1 prevalent vertebral fracture.
Purpose Introduction
Impaired physical performance and sarcopenia are associated with increased fracture risk. This study aims to assess physical performance and the prevalence of sarcopenia in patients with a recent clinical fracture attending the Fracture Liaison Service (FLS) compared to population means.
Methods
In this cross-sectional study, chair stand test (CST), handgrip strength (HGS), timed-up-and-go (TUG), 6-min walking-test (6MWT), and sarcopenia (following EWGSOP2) were assessed. The proportion of patients with impaired/poor performance compared to reference data was calculated (Z-score: ≥ − 2SD to < − 1 (impaired) and < − 2 SD (poor)). Associations of fracture type, sex, age, and time since fracture with Z-scores were assessed using linear regression analyses.
Results
A total of 1789 consecutive FLS patients were included (median age (IQR): 66 (59–74), 70.7% females, 3.9 (± 1.6) months after fracture). The prevalence of impaired/poor performance for CST, HGS, TUG, and 6MWT was 39.2%, 30.4%, 21.9%, and 71.5%, respectively (expected proportion of 16%) and 2.8% had sarcopenia. Lower Z-scores (
P
< 0.001) were found for hip, major, and ≥ 1 prevalent vertebral fracture (VF) in CST (major: regression coefficient (
B
) (95%CI) = − 0.25 − 0.34, − 0.16; hip:
B
= − 0.32 − 0.47, − 0.17, VF:
B
= − 0.22 − 0.34, − 0.11), TUG; (major:
B
= − 0.54 − 0.75, − 0.33; hip:
B
= − 1.72 − 2.08, -1.35, VF:
B
= − 0.61 − 0.88, − 0.57), 6MWT (major:
B
= − 0.34 − 0.47, − 0.21; hip:
B
= − 0.99 − 1,22, − 0.77, VF:
B
= − 0.36 − 0.53, − 0.19).
Conclusions
Physical performance is significantly lower in FLS patients compared to healthy peers, especially in patients with hip, major or prevalent VF. These findings underline the need to assess and improve the physical performance of FLS patients, despite a low prevalence of sarcopenia.
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