Combined results from different independent studies suggest that acclimatization to high altitude induces a slowly developing sympathetic activation, even at levels of hypoxia that cause no acute ...chemoreflex‐mediated sympathoexcitation. We here provide direct neurophysiological evidence for this phenomenon. In eight Danish lowlanders, we quantified mean arterial blood pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA), twice at sea level (normoxia and with acute hypoxic exposure to 12.6% O2) and twice at high altitude (after 10 and 50 days of exposure to 4100 m). Measurements were also obtained in eight Bolivian highlanders on one occasion at high altitude. Acute hypoxic exposure caused no increase in MSNA (15 ± 2 vs 16 ± 2 bursts per min, respectively, and also MAP and HR remained stable). In contrast, from sea level to 10 and 50 days in high‐altitude increases were observed in MAP: 72 ± 2 vs 78 ± 2 and 75 ± 2 mm Hg; HR: 54 ± 3 vs 67 ± 3 and 65 ± 3 beats per min; MSNA: 15 ± 2 vs 42 ± 5 and 42 ± 5 bursts per min, all P < .05. Bolivian subjects had high levels of MSNA: 34 ± 4 bursts per min. The simultaneous increase in MAP, HR, and MSNA suggests high altitude‐induced sympathetic activity, which is sustained in well‐acclimatized lowlanders. The high MSNA levels in the Bolivian highlanders suggest lifelong sympathetic activation at high altitude.
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BFBNIB, FSPLJ, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited ...statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aseptic loosening is the dominant failure mechanism in contemporary knee replacement surgery, but diagnostic techniques are poorly sensitive to the early stages of loosening and poorly specific in ...delineating aseptic cases from infections. Smart implants have been proposed as a solution, but incorporating components for sensing, powering, processing, and communication increases device cost, size, and risk; hence, minimising onboard instrumentation is desirable. In this study, two wireless, battery-free smart implants were developed that used passive biotelemetry to measure fixation at the implant-cement interface of the tibial components. The sensing system comprised of a piezoelectric transducer and coil, with the transducer affixed to the superior surface of the tibial trays of both partial (PKR) and total knee replacement (TKR) systems. Fixation was measured via pulse-echo responses elicited via a three-coil inductive link. The instrumented systems could detect loss of fixation when the implants were partially debonded (+7.1% PKA, +32.6% TKA, both
< 0.001) and fully debonded in situ (+6.3% PKA, +32.5% TKA, both
< 0.001). Measurements were robust to variations in positioning of the external reader, soft tissue, and the femoral component. With low cost and small form factor, the smart implant concept could be adopted for clinical use, particularly for generating an understanding of uncertain aseptic loosening mechanisms.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Arthrogryposis multiplex congenita (AMC) has been described and defined in thousands of articles, but the terminology used has been inconsistent in clinical and research communities. A definition of ...AMC was recently developed using a modified Delphi consensus method involving 25 experts in the field of AMC from 8 countries. Participants included health care professionals, researchers, and individuals with AMC. An annotation of the definition provides more in‐depth explanations of the different sentences of the AMC definition and is useful to complement the proposed definition. The aim of this study was to provide an annotation of the proposed consensus‐based AMC definition. For the annotation process, 17 experts in AMC representing 10 disciplines across 7 countries participated. A paragraph was developed for each sentence of the definition using an iterative process involving multiple authors with varied and complementary expertise, ensuring all points of view were taken into consideration. The annotated definition provides an overview of the different topics related to AMC and is intended for all stakeholders, including youth and adults with AMC, their families, and clinicians and researchers, with the hopes of unifying the understanding of AMC in the international community.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aim
It is an ongoing discussion the extent to which oxygen delivery and oxygen extraction contribute to an increased muscle oxygen uptake during dynamic exercise. It has been proposed that local ...muscle factors including the capillary bed and mitochondrial oxidative capacity play a large role in prolonged low‐intensity training of a small muscle group when the cardiac output capacity is not directly limiting. The purpose of this study was to investigate the relative roles of circulatory and muscle metabolic mechanisms by which prolonged low‐intensity exercise training alters regional muscle VO2.
Methods
In nine healthy volunteers (seven males, two females), haemodynamic and metabolic responses to incremental arm cycling were measured by the Fick method and biopsy of the deltoid and triceps muscles before and after 42 days of skiing for 6 h day−1 at 60% max heart rate.
Results
Peak pulmonary VO2 during arm crank was unchanged after training (2.38 ± 0.19 vs. 2.18 ± 0.2 L min−1 pre‐training) yet arm VO2 (1.04 ± 0.08 vs. 0.83 ± 0.1 L min1, P < 0.05) and power output (137 ± 9 vs. 114 ± 10 Watts) were increased along with a higher arm blood flow (7.9 ± 0.5 vs. 6.8 ± 0.6 L min−1, P < 0.05) and expanded muscle capillary volume (76 ± 7 vs. 62 ± 4 mL, P < 0.05). Muscle O2 diffusion capacity (16.2 ± 1 vs. 12.5 ± 0.9 mL min−1 mHg−1, P < 0.05) and O2 extraction (68 ± 1 vs. 62 ± 1%, P < 0.05) were enhanced at a similar mean capillary transit time (569 ± 43 vs. 564 ± 31 ms) and P50 (35.8 ± 0.7 vs. 35 ± 0.8), whereas mitochondrial O2 flux capacity was unchanged (147 ± 6 mL kg min−1 vs. 146 ± 8 mL kg min−1).
Conclusion
The mechanisms underlying the increase in peak arm VO2 with prolonged low‐intensity training in previously untrained subjects are an increased convective O2 delivery specifically to the muscles of the arm combined with a larger capillary–muscle surface area that enhance diffusional O2 conductance, with no apparent role of mitochondrial respiratory capacity.
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DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The burden of foodborne disease is not well defined in many countries or regions or on a global level. The World Health Organization (WHO), in conjunction with other national public health agencies, ...is coordinating a number of international activities designed to assist countries in the strengthening of disease surveillance and to determine the burden of acute gastroenteritis. These data can then be used to estimate the following situations: (1) the burden associated with acute gastroenteritis of foodborne origin, (2) the burden caused by specific pathogens commonly transmitted by food, and (3) the burden caused by specific foods or food groups. Many of the scientists collaborating with the WHO on these activities have been involved in quantifying the burden of acute gastroenteritis on a national basis. This article reviews these key national studies and the international efforts that are providing the necessary information and technical resources to derive national, regional, and global burden of disease estimates.
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BFBNIB, NUK, PNG, UL, UM, UPUK
Cartilage collagen has very limited repair potential, though some turnover and incorporation has not been fully excluded. We aim to determine the regional turnover of human osteoarthritis cartilage.
...Patients scheduled for knee joint replacement surgery due to osteoarthritis were recruited in this prospective study of four weeks duration. Deuterium oxide (D2O) was administered orally by weekly boluses at 70% D2O, initially 150 ml followed by three boluses of 50 ml. Cartilage from the medial tibia plateau was sampled centrally, under the meniscus, and from osteophytes and treated enzymatically with hyaluronidase and trypsin. Samples were analysed for deuterium incorporation in alanine using mass spectrometry and for gene expression by real-time reverse transcriptase polymerase chain reaction.
Twenty participants completed the study: mean (SD) age 64 ± 9.1 years, 45% female, BMI 29.5 ± 4.8 kg/m2. Enzymatically treated cartilage from central and submeniscal regions showed similar enrichments at 0.063% APE, while osteophytes showed significantly greater enrichment at 0.072% APE (95% confidence interval of difference) 0.004–0.015). Fractional synthesis rates were similar for central 0.027%/day and submeniscal cartilage 0.022%/day but 10-fold higher in osteophytes 0.22%/day 0.098–0.363. When compared to central cartilage, submeniscal cartilage had increased gene expression of MMP-3 and decreased lubricin expression. Untreated cartilage had higher turnover (enrichments at 0.073% APE) than enzymatically treated cartilage (0.063% APE).
In OA, despite regional differences in gene expression, the turnover of the articular cartilage matrix across the entire joint surface is very limited, but higher turnover was observed in osteophyte cartilage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Combining endurance and strength training in the same session has been reported to reduce the anabolic response to the latter form of exercise. The underlying mechanism, based primarily on results ...from rodent muscle, is proposed to involve AMPK-dependent inhibition of mTORC1 signaling. This hypothesis was tested in eight trained male subjects who in randomized order performed either resistance exercise only (R) or interval cycling followed by resistance exercise (ER). Biopsies taken from the vastus lateralis before and after endurance exercise and repeatedly after resistance exercise were assessed for glycogen content, kinase activity, protein phosphorylation, and gene expression. Mixed muscle fractional synthetic rate was measured at rest and during 3 h of recovery using the stable isotope technique. In ER, AMPK activity was elevated immediately after both endurance and resistance exercise (∼90%, P < 0.05) but was unchanged in R. Thr(389) phosphorylation of S6K1 was increased severalfold immediately after exercise (P < 0.05) in both trials and increased further throughout recovery. After 90 and 180 min recovery, S6K1 activity was elevated (∼55 and ∼110%, respectively, P < 0.05) and eukaryotic elongation factor 2 phosphorylation was reduced (∼55%, P < 0.05) with no difference between trials. In contrast, markers for protein catabolism were differently influenced by the two modes of exercise; ER induced a significant increase in gene and protein expression of MuRF1 (P < 0.05), which was not observed following R exercise only. In conclusion, cycling-induced elevation in AMPK activity does not inhibit mTOR complex 1 signaling after subsequent resistance exercise but may instead interfere with the hypertrophic response by influencing key components in protein breakdown.
Genetics and Classifications Hall, Judith G; Kimber, Eva; van Bosse, Harold J P
Journal of pediatric orthopaedics,
2017-July/August, Volume:
37 Suppl 1, Issue:
Supplement 1
Journal Article
Peer reviewed
Arthrogryposis multiplex congenital (AMC) is a descriptive term for a group of conditions that all share the characteristic of congenital contractures. There are an estimated 400 discrete diagnoses ...that can lead to a child being born with arthrogryposis. The 2 biggest categories of conditions are amyoplasia and distal arthrogryposis, which combined make up ∼50% to 65% of all diagnoses within the AMC subset. Amyoplasia, the most common AMC condition, seems to be a nongenetic syndrome, leading to very characteristic upper and lower limb contractures. The distal arthrogryposes, in contrast, have an underlying genetic abnormality, which in many cases seems to target the fast twitch muscles of the developing fetus. Classifying AMC is a difficult task, given the broad range of conditions represented. Four different classification schemes are presented.
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