IMPORTANCE: Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly ...lasting effects of methylphenidate on the human dopaminergic system. OBJECTIVES: To determine whether the effects of methylphenidate on the dopaminergic system are modified by age and to test the hypothesis that methylphenidate treatment of young but not adult patients with ADHD induces lasting effects on the cerebral blood flow response to dopamine challenge, a noninvasive probe for dopamine function. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain–Methylphenidate) among ADHD referral centers in the greater Amsterdam area in the Netherlands between June 1, 2011, and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12 years or 23 to 40 years, and stimulant treatment–naive status. INTERVENTIONS: Treatment with either methylphenidate or a matched placebo for 16 weeks. MAIN OUTCOMES AND MEASURES: Change in the cerebral blood flow response to an acute challenge with methylphenidate, noninvasively assessed using pharmacological magnetic resonance imaging, between baseline and 1 week after treatment. Data were analyzed using intent-to-treat analyses. RESULTS: Among 131 individuals screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50 participants were randomized to receive methylphenidate and 49 to placebo. Sixteen weeks of methylphenidate treatment increased the cerebral blood flow response to methylphenidate within the thalamus (mean difference, 6.5; 95% CI, 0.4-12.6; P = .04) of children aged 10 to 12 years old but not in adults or in the placebo group. In the striatum, the methylphenidate condition differed significantly from placebo in children but not in adults (mean difference, 7.7; 95% CI, 0.7-14.8; P = .03). CONCLUSIONS AND RELEVANCE: We confirm preclinical data and demonstrate age-dependent effects of methylphenidate treatment on human extracellular dopamine striatal-thalamic circuitry. Given its societal relevance, these data warrant replication in larger groups with longer follow-up. TRIAL REGISTRATION: identifier: NL34509.000.10 and trialregister.nl identifier: NTR3103.
The kidney is a highly metabolic organ that requires substantial adenosine triphosphate for the active transport required to maintain water and solute reabsorption. Aberrations in energy availability ...and energy utilization can lead to cellular dysfunction and death. Mitochondria are essential for efficient energy production. The pathogenesis of acute kidney injury is complex and varies with different types of injury. However, multiple distinct acute kidney injury syndromes share a common dysregulation of energy metabolism. Pathways of energy metabolism and mitochondrial dysfunction are emerging as critical drivers of acute kidney injury and represent new potential targets for treatment. This review shows the basic metabolic pathways that all cells depend on for life; describes how the kidney optimizes those pathways to meet its anatomic, physiologic, and metabolic needs; summarizes the importance of metabolic and mitochondrial dysfunction in acute kidney injury; and analyzes the mitochondrial processes that become dysregulated in acute kidney injury including mitochondrial dynamics, mitophagy, mitochondrial biogenesis, and changes in mitochondrial energy metabolism.
Anatomy of the Vascularized Lateral Femoral Condyle Flap Parvizi, Daryousch; Vasilyeva, Anna; Wurzer, Paul ...
Plastic and reconstructive surgery (1963),
2016-June, 2016-Jun, 2016-06-00, 20160601, Letnik:
137, Številka:
6
Journal Article
Recenzirano
BACKGROUND:The perforators of the free lateral femoral condyle flap have yet to be adequately described in humans. Therefore, the authors investigated the perforator vessels of the lateral femoral ...condyle flap in an anatomical study and discussed potential clinical applications with a particular interest in its indication with vascularized bone and/or iliotibial band for tendon repair surgery.
METHODS:The authors dissected thighs of 28 cadavers to evaluate the anatomical properties of perforator vessels that branch from the superior lateral genicular artery and supply bone, cartilage, subcutaneous tissue, and the iliotibial band of the lateral femoral condyle.
RESULTS:In each dissected thigh, the superior lateral genicular artery was present and the average pedicle length was 38 ± 10 mm. The average diameter of the superior lateral genicular artery, proximal to its distribution into the deep articular and superficial patellar branches, was 2 ± 0.5 mm. A communication between deep articular and superficial patellar branches was seen in 96 percent of the dissected thighs. In 24 cases (86 percent), the authors were able to show the iliotibial band perforating vessel and harvest a free lateral femoral condyle flap as an osteochondral fasciocutaneous bone flap with vascularized tendon.
CONCLUSIONS:Altogether, the authors’ results indicate that the blood supply of the lateral femoral condyle flap is consistent and the lateral femoral condyle flap could serve as a free composite flap for complex indications in hand or limb reconstructive surgery. Clinical studies to compare the lateral femoral condyle to other well-established microsurgical free flaps are warranted.
Human splanchnic amino-acid metabolism Neis, Evelien P. J. G.; Sabrkhany, S.; Hundscheid, I. ...
Amino acids,
01/2017, Letnik:
49, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Plasma levels of several amino acids are correlated with metabolic dysregulation in obesity and type 2 diabetes. To increase our understanding of human amino-acid metabolism, we aimed to determine ...splanchnic interorgan amino-acid handling. Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy were included in this study. Blood was sampled from the portal vein, hepatic vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal vein, and the radial artery during surgery. The difference between arterial and venous concentrations of 21 amino acids was determined using liquid chromatography as a measure of amino-acid metabolism across a given organ. Whereas glutamine was significantly taken up by the small intestine (121.0 ± 23.8 µmol/L;
P
< 0.0001), citrulline was released (−36.1 ± 4.6 µmol/L;
P
< 0.0001). This, however, was not seen for the colon. Interestingly, the liver showed a small, but a significant uptake of citrulline from the circulation (4.8 ± 1.6 µmol/L;
P
= 0.0138) next to many other amino acids. The kidneys showed a marked release of serine and alanine into the circulation (−58.0 ± 4.4 µmol/L and −61.8 ± 5.2 µmol/L,
P
< 0.0001), and a smaller, but statistically significant release of tyrosine (−12.0 ± 1.3 µmol/L,
P
< 0.0001). The spleen only released taurine (−9.6 ± 3.3 µmol/L;
P
= 0.0078). Simultaneous blood sampling in different veins provides unique qualitative and quantitative information on integrative amino-acid physiology, and reveals that the well-known intestinal glutamine–citrulline pathway appears to be functional in the small intestine but not in the colon.
Highlights • Sonography of the peripheral nervous system reveals multifocal nerve enlargement in the majority of chronic inflammatory demyelinating polyneuropathy (CIDP) patients. • Sonographic nerve ...enlargement in CIDP is related with clinical severity. • Increased nerve vascularization, a possible marker for diseases activity, can be detected in CIDP, especially in enlarged nerves.
BACKGROUND:Abdominal flap reconstruction is the most popular form of autologous breast reconstruction. The current study compared complications and patient-reported outcomes after pedicled transverse ...rectus abdominis myocutaneous (TRAM), free TRAM, deep inferior epigastric perforator (DIEP), and superficial inferior epigastric artery (SIEA) flaps.
METHODS:Patients undergoing abdominally based breast reconstruction at 11 centers were prospectively evaluated for abdominal donor-site and breast complications. Patient-reported outcomes were measured by the BREAST-Q and Patient-Reported Outcomes Measurement Information System surveys. Mixed-effects regression models were used to assess the effects of procedure type on outcomes.
RESULTS:Seven hundred twenty patients had 1-year follow-up and 587 had 2-year follow-up. Two years after reconstruction, SIEA compared with DIEP flaps were associated with a higher rate of donor-site complications (OR, 2.7; p = 0.001); however, SIEA flaps were associated with higher BREAST-Q abdominal physical well-being scores compared with DIEP flaps at 1 year (mean difference, 4.72, on a scale from 0 to 100; p = 0.053). This difference was not significant at 2 years. Abdominal physical well-being scores at 2 years postoperatively were lower in the pedicled TRAM flap group by 7.2 points (p = 0.006) compared with DIEP flaps and by 7.8 points (p = 0.03) compared with SIEA flaps, and in the free TRAM flap group, scores were lower by 4.9 points (p = 0.04) compared with DIEP flaps. Bilateral reconstruction had significantly lower abdominal physical well-being scores compared with unilateral reconstruction.
CONCLUSIONS:Although all abdominally based flaps are viable breast reconstruction options, DIEP and SIEA flaps are associated with higher abdominal physical well-being than pedicled and free TRAM flaps. Although SIEA flaps offer the advantage of not violating the fascia, higher rates of donor-site complications may diminish patient satisfaction.
CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, II.
The increase in working memory (WM) capacity is an important part of cognitive development during childhood and adolescence. Cross-sectional analyses have associated this development with higher ...activity, thinner cortex, and white matter maturation in fronto-parietal networks. However, there is still a lack of longitudinal data showing the dynamics of this development and the role of subcortical structures. We included 89 individuals, aged 6-25 years, who were scanned 1-3 times at 2-year intervals. Functional magnetic resonance imaging (fMRI) was used to identify activated areas in superior frontal, intraparietal cortices, and caudate nucleus during performance on a visuo-spatial WM task. Probabilistic tractography determined the anatomical pathways between these regions. In the cross-sectional analysis, WM capacity correlated with activity in frontal and parietal regions, cortical thickness in parietal cortex, and white matter structure both fractional anisotropy (FA) and white matter volume of fronto-parietal and fronto-striatal tracts. However, in the longitudinal analysis, FA in white matter tracts and activity in caudate predicted future WM capacity. The results show a dynamic of neural networks underlying WM development in which cortical activity and structure relate to current capacity, while white matter tracts and caudate activity predict future WM capacity.
Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting-state functional connectivity MRI reports have implicated ...regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: (1) finding network nodes that participate in multiple subnetworks of the brain, and (2) finding spatial locations in which several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity.
•Reveals confounds in degree-based hub detection techniques in correlation networks•Utilizes multiple methods to convergently identify hubs in correlation networks•Identifies regions and nodes that support and link different parts of brain networks•Generates differential, testable, and spatially constrained hypotheses regarding hubs
Power et al. describe methods to find influential nodes in correlation networks. These methods identify places in the human brain where lesions may disrupt many types of processing (e.g., perception, memory, attention) and regions where lesions may disrupt relatively few processes.
BACKGROUND:Improper manipulation of injectable treatments to the face can result in disastrous vascular complications. The aim of the present study was to elucidate the detoured course of the facial ...artery and to provide detailed metric data regarding facial artery location with a view to helping physicians avoid iatrogenic vascular accidents during injectable treatments.
METHODS:Sixty specimens from 35 embalmed cadavers (24 male and 11 female cadavers; mean age, 70.0 years) and one fresh male cadaver (age, 62 years) were used for this study.
RESULTS:In 56 cases (93.3 percent), the branches of the facial artery were observed at the vicinity of the nasolabial fold. The facial artery was located 3.2 ± 4.5 mm (mean ± SD) lateral to the ala of the nose and 13.5 ± 5.4 mm lateral to the oral commissure. It crossed the nasolabial fold in 33.9 percent of cases, and ascended within 5 mm of the nasolabial fold in 42.9 percent. The facial artery and detoured branches were found in 18 cases (30.0 percent). In the cases with detoured branches, the facial artery turned medially over the infraorbital area at 39.2 ± 5.8 mm lateral to the facial midsagittal line and 35.2 ± 8.2 mm inferior to the plane connecting the medial epicanthi of both sides. The nasojugal portion of the detoured branch traveled along the inferior border of the orbicularis oculi and then ascended toward the forehead, forming the angular artery.
CONCLUSION:This detailed vascular anatomy of the facial artery will promote safe clinical manipulations during injectable treatments to the nasolabial fold and nasojugal groove.
The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and ...the dura mater is crucial for waste clearance and immune surveillance
. How the arachnoid barrier balances separation and communication is poorly understood. Here, using transcriptomic data, we developed transgenic mice to examine specific anatomical structures that function as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, magnetic resonance imaging tracers transit along bridging veins in a similar manner to access the subarachnoid space. Notably, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also enable cellular trafficking, representing a route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that link the central nervous system with the dura and its immunological diversity and waste clearance systems.
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