Geochronological challenges posed by continuously developing tectonometamorphic systems: insights from Rb–Sr mica ages from the Cycladic Blueschist Belt, Syros (Greece).

Is metamorphism and its causative tectonics best viewed as a series of punctuated events or as a continuum? This question is addressed through examination of the timing of exhumation of the Cycladic Blueschist Belt (CBB). The cause of scatter beyond analytical error in Rb–Sr geochronology was investigated using a suite of 39 phengite samples. Rb–Sr ages have been measured on phengite microsamples drilled from specific microstructures in thin sections of calcschists and metabasites from the CBB on Syros. The majority are from samples that have well-preserved blueschist facies mineral assemblages with limited greenschist facies overprint. The peak metamorphic temperatures involved are below the closure temperature for white mica so that crystallization ages are expected to be preserved. This is supported by the coexistence of different ages in microstructures of different relative age; in one sample phengite from the dominant extensional blueschist facies fabric preserves an age of 35 Ma while post-tectonic mica, millimetres away, has an age of 26 Ma. The results suggest that micro-sampling techniques linked to detailed microstructural analysis are critical to understanding the timing and duration of deformation in tectonometamorphic systems. North of the Serpentinite Belt in northern Syros, phengite Rb–Sr ages are generally between 53 and 46 Ma, comparable to previous dates from this area. South of the Serpentinite Belt phengite in blueschist facies assemblages associated with extensional fabrics linked to exhumation have ages that range from 42 Ma down to c. 30 Ma indicating that extensional deformation while still under blueschist facies conditions continued until 30 Ma. No age measurements on samples with unambiguous evidence of deformation under greenschist facies conditions were made; two rocks with greenschist facies assemblages gave phengite ages that overlap with the younger blueschist samples, suggesting blueschist facies phengite is preserved in these rocks. Two samples yielded ages below 27 Ma; one is from a post-tectonic microstructure, the other from a greenschist in which the fabric developed during earlier blueschist facies conditions. These ages are consistent with previous evidence of greenschist facies conditions from c. 25 Ma onwards. The data are consistent with a model of deformation that is continuous on a regional scale

Involvement of N-methyl-D-aspartate receptors in plasticity induced by paired corticospinal-motoneuronal stimulation in humans

Plasticity can be induced at human corticospinalmotoneuronal synapses by delivery of repeated, paired stimuli to corticospinal axons and motoneurons in a technique called paired corticospinal-motoneuronal stimulation (PCMS). To date, the mechanisms of the induced plasticity are unknown. To determine whether PCMS-induced plasticity is dependent on N-methyl-D-aspartate receptors (NMDARs), the effect of the noncompetitive NMDAR antagonist dextromethorphan on PCMS-induced facilitation was assessed in a 2-day, double-blind, placebo-controlled experiment. PCMS consisted of 100 pairs of stimuli, delivered at an interstimulus interval that produces facilitation at corticospinal-motoneuronal synapses that excite biceps brachii motoneurons. Transcranial magnetic stimulation elicited corticospinal volleys, which were timed to arrive at corticospinal-motoneuronal synapses just before antidromic potentials elicited in motoneurons with electrical brachial plexus stimulation. To measure changes in the corticospinal pathway at a spinal level, biceps responses to cervicomedullary stimulation (cervicomedullary motor evoked potentials, CMEPs) were measured before and for 30 min after PCMS. Individuals who displayed a ≥10% increase in CMEP size after PCMS on screening were eligible to take part in the 2-day experiment. After PCMS, there was a significant difference in CMEP area between placebo and dextromethorphan days (P ~ 0.014). On the placebo day PCMS increased average CMEP areas to 127 = 46% of baseline, whereas on the dextromethorphan day CMEP area was decreased to 86 = 33% of baseline (mean = SD; placebo: n ~ 11, dextromethorphan: n ~ 10). Therefore, dextromethorphan suppressed the facilitation of CMEPs after PCMS. This indicates that plasticity induced at synapses in the human spinal cord by PCMS may be dependent on NMDARs. NEW & NOTEWORTHY Paired corticospinal-motoneuronal stimulation can strengthen the synaptic connections between corticospinal axons and motoneurons at a spinal level in humans. The mechanism of the induced plasticity is unknown. In our 2-day, double-blind, placebo-controlled study we show that the N-methyl-D-aspartate receptor (NMDAR) antagonist dextromethorphan suppressed plasticity induced by paired corticospinal-motoneuronal stimulation, suggesting that an NMDAR-dependent mechanism is involved

Recent advances using FcRn overexpression in transgenic animals to overcome impediments of standard antibody technologies to improve the generation of specific antibodies.

This review illustrates the salutary effects of neonatal Fc receptor (FcRn) overexpression in significantly improving humoral immune responses in the generation of antibodies for immunotherapy and diagnostics. These include: (1) improved IgG protection; (2) augmented antigen-specific humoral immune response with larger numbers of antigen specific B cells, thus offering a wider spectrum of clones; (3) generation of antibodies against weakly immunogenic antigens; (4) significant improvements in the number and substantial developments in the diversity of hybridomas. FcRn transgenesis thus confers a number of practical benefits, including faster antibody production, higher antibody yields and improved generation of hybridomas for monoclonal antibody production. Notably, these efficiencies in polyclonal antibody production were also demonstrated in FcRn transgenic rabbits. Overall, FcRn transgenic animals yield more antibodies and provide a route to the generation of antibodies against antigens of low immunogenicity that are difficult to obtain using currently available methods

The detection and sensory perception of inspiratory resistive loads in people with chronic tetraplegia

This study investigated sensations of breathing following tetraplegia. Fifteen people with chronic tetraplegia and fifteen healthy able-bodied controls matched for age, sex, height, and weight participated. Sensations of breathing were quantified by determining the threshold for detecting an added resistance during inspiration. In a separate task, the perceived magnitudes of six suprathreshold resistive loads were determined with a modified Borg scale. The detection threshold of 0.34 cmH2O/L/s [standard deviation (SD) 0.14] in the tetraplegia group was higher than the 0.23 cmH2O/L/s (SD 0.10) threshold for able-bodied controls (P = 0.004). Both participant groups perceived larger loads to be more effortful, with the Borg effort rating increasing linearly with the peak inspiratory pressure generated at each load. The relationship between Borg effort rating and peak inspiratory pressure was steeper in participants with tetraplegia than in able-bodied controls (P = 0.001), but there was no difference when pressure was divided by maximal inspiratory pressure (P = 0.95). Despite a higher detection threshold, the findings suggest that the perceived magnitude of a suprathreshold inspiratory load is not impaired in chronic tetraplegia and that load magnitude perception is related to the maximal, and not absolute, inspiratory muscle force. NEW & NOTEWORTHY Sensations of breathing are thought to be impaired following chronic tetraplegia. The detection threshold for an added resistive load during inspiration was higher in people with tetraplegia than in healthy able-bodied participants. However, for inspiratory loads above the detection threshold, the perceived magnitude of a resistive load as a function of the peak inspiratory pressure was greater in tetraplegia. Load magnitude perception was comparable between participant groups when peak pressure was divided by maximal inspiratory pressure

Optimal electrode position for abdominal functional electrical stimulation

Abdominal functional electrical stimulation (abdominal FES) improves respiratory function. Despite this, clinical use remains low, possibly due to lack of agreement on the optimal electrode position. This study aimed to ascertain the optimal electrode position for abdominal FES, assessed by expiratory twitch pressure. Ten able-bodied participants received abdominal FES using electrodes placed: 1) on the posterolateral abdominal wall and at the motor points of 2) the external oblique muscles plus rectus abdominis muscles, and 3) the external obliques alone. Gastric (Pga) and esophageal (Pes) twitch pressures were measured using a gastroesophageal catheter. Single-stimulation pulses were applied at functional residual capacity during step increments in stimulation current to maximal tolerance or until Pga plateaued. Stimulation applied on the posterolateral abdominal wall led to a 71% and 53% increase in Pga and Pes, respectively.compared with stimulation of the external oblique and rectus abdominis muscles (P < 0.001) and a 95% and 56% increase in Pga and Pes, respectively.compared with stimulation of the external oblique muscles alone (P < 0.001). Stimulation of both the external oblique and rectus abdominis muscles led to an 18.3% decrease in Pg.compared with stimulation of only the external oblique muscles (P = 0.040), with inclusion of the rectus abdominis having no effect on Pes (P = 0.809). Abdominal FES applied on the posterolateral abdominal wall generated the highest expiratory twitch pressures. As expiratory pressure is a good indicator of expiratory muscle strength and, thus, cough efficacy, we recommend this electrode position for all therapeutic applications of abdominal FES. NEW & NOTEWORTHY While abdominal functional electrical stimulation (abdominal FES) can improve respiratory function, clinical use remains low. This is at least partly due to lack of agreement on the optimal electrode position. Therefore, this study aimed to ascertain the optimal electrode position for abdominal FES. We show that electrodes placed on the posterolateral abdominal wall generated the highest expiratory twitch pressures. As such, we recommend this electrode position for all therapeutic applications of abdominal FES

The reliability of inspiratory resistive load magnitude and detection testing

Objectives: To assess the test-retest reliability of inspiratory load detection and load magnitude perception tests in healthy volunteers. Design: Cohort of convenience. Setting: Respiratory physiology laboratory. Participants: Twenty healthy adults. Interventions: On two separate occasions participants performed tests of inspiratory loading. Participants breathed through custom made resistive tubing and were asked to indicate when they detected a different resistance during inspiration. In a second test participants rated the magnitude of presented inspiratory loads using the modified Borg score. Main Outcome Measures: Intra-class Correlation Coefficient (ICC2,1) values for repeated tests of inspiratory load detection threshold and load magnitude rating. Results: ICC2,1 values ranged from 0.657–0.786 for load detection testing and 0.739 to 0.969 for rating of load magnitude. Conclusions: The tests are simple and reliable measures of inspiratory load detection and magnitude rating. They can be used in future research to determine the effectiveness of interventions to reduce the effort of breathing in health and disease

Muscle fiber and motor unit behavior in the longest human skeletal muscle

The sartorius muscle is the longest muscle in the human body. It is strap-like, up to 600 mm in length, and contains five to seven neurovascular compartments, each with a neuromuscular endplate zone. Some of its fibers terminate intrafascicularly, whereas others may run the full length of the muscle. To assess the location and timing of activation within motor units of this long muscle, we recorded electromyographic potentials from multiple intramuscular electrodes along sartorius muscle during steady voluntary contraction and analyzed their activity with spike-triggered averaging from a needle electrode inserted near the proximal end of the muscle. Approximately 30% of sartorius motor units included muscle fibers that ran the full length of the muscle, conducting action potentials at 3.9 +/- 0.1 m/s. Most motor units were innervated within a single muscle endplate zone that was not necessarily near the midpoint of the fiber. As a consequence, action potentials reached the distal end of a unit as late as 100 ms after initiation at an endplate zone. Thus, contractile activity is not synchronized along the length of single sartorius fibers. We postulate that lateral transmission of force from fiber to endomysium and a wide distribution of motor unit endplates along the muscle are critical for the efficient transmission of force from sarcomere to tendon and for the prevention of muscle injury caused by overextension of inactive regions of muscle fibers

Supraspinal fatigue in human inspiratory muscles with repeated sustained maximal efforts

To investigate the involvement of supraspinal fatigue in the loss of maximal inspiratory pressure (PImax), we fatigued the inspiratory muscles. Six participants performed 5 sustained maximal isometric inspiratory efforts (15-s contractions, duty cycle ~75%) which reduced PImax, as measured from esophageal and mouth pressure, to around half of their initial maximums. Transcranial magnetic stimulation (TMS) delivered over the motor cortex near the beginning and end of each maximal effort evoked superimposed twitch-like increments in the ongoing PImax, increasing from ~1.0% of PImax in the unfatigued contractions to ≥40% of ongoing PImax for esophageal and mouth pressures. The rate of increase in the superimposed twitch as PImax decreased with fatigue was not significantly different between the esophageal and mouth pressure measures. The inverse relationship between superimposed twitch pressure and PImax indicates a progressive decline in the ability of motor cortical output to drive the inspiratory muscles maximally, leading to the development of supraspinal fatigue. TMS also evoked silent periods in the electromyographic recordings of diaphragm, scalenes, and parasternal intercostal. The duration of the silent period increased with fatigue in all three muscles, which suggests greater intracortical inhibition, with the largest change observed in the diaphragm. The peak rate of relaxation in pressure during the silent period slowed as fatigue developed, indicating peripheral contractile changes in the active inspiratory muscles. These changes in the markers of fatigue show that both central and peripheral fatigue contribute to the loss in PImax when inspiratory muscles are fatigued with repeated sustained maximal efforts. NEW & NOTEWORTHY When the inspiratory muscles are fatigued with repeated sustained maximal efforts, supraspinal fatigue, a component of central fatigue, contributes to the loss in maximal inspiratory pressure. The presence of supraspinal fatigue was confirmed by the increase in amplitude of twitch-like increments in pressure evoked by motor cortical stimulation during maximal efforts, indicating that motor cortical output was not maximal as extra muscle force could be generated to increase inspiratory pressure

Direct procurement of donor heart with normothermic regional perfusion of abdominal organs.

PURPOSE: To evaluate if direct procurement of heart is possible in combination with normothermic regional perfusion of abdominal organs in donors after circulatory death. DESCRIPTION: A donation after circulatory death pathway was utilized for a 41-year-old female following an irreversible brain injury. After meeting criteria for the organ donation, heart was retrieved and re-animated on ex-situ perfusion system while abdominal organs were perfused using normothermic regional perfusion. EVALUATION: All the donated organs and their recipients had excellent short-term outcome. CONCLUSIONS: We demonstrated a successful combination of direct procurement of the heart and normothermic regional perfusion of the abdominal organs