Nocturnal swallowing augments arousal intensity and arousal tachycardia.

Cortical arousal from sleep is associated with autonomic activation and acute increases in heart rate. Arousals vary considerably in their frequency, intensity/duration, and physiological effects. Sleep and arousability impact health acutely (daytime cognitive function) and long-term (cardiovascular outcomes). Yet factors that modify the arousal intensity and autonomic activity remain enigmatic. In this study of healthy human adults, we examined whether reflex airway defense mechanisms, specifically swallowing or glottic adduction, influenced cardiac autonomic activity and cortical arousal from sleep. We found, in all subjects, that swallows trigger rapid, robust, and patterned tachycardia conserved across wake, sleep, and arousal states. Tachycardia onset was temporally matched to glottic adduction-the first phase of swallow motor program. Multiple swallows increase the magnitude of tachycardia via temporal summation, and blood pressure increases as a function of the degree of tachycardia. During sleep, swallows were overwhelmingly associated with arousal. Critically, swallows were causally linked to the intense, prolonged cortical arousals and marked tachycardia. Arousal duration and tachycardia increased in parallel as a function of swallow incidence. Our findings suggest that cortical feedback and tachycardia are integrated responses of the swallow motor program. Our work highlights the functional influence of episodic, involuntary airway defense reflexes on sleep and vigilance and cardiovascular function in healthy individuals.

Discharge properties of human diaphragm motor units with ageing.

KEY POINTS: Ageing is associated with changes in the respiratory system including in the lungs, rib cage and muscles. Neural drive to the diaphragm, the principal inspiratory muscle, has been reported to increase during quiet breathing with ageing. We demonstrated that low-threshold motor units of the human diaphragm recruited during quiet breathing have similar discharge frequencies across age groups and shorter discharge times in older age. With ageing, motor unit action potential area increased. We propose that there are minimal functionally significant changes in the discharge properties of diaphragm motor units with ageing despite remodelling of the motor unit in the periphery. ABSTRACT: There are changes in the skeletal, pulmonary and respiratory neuromuscular systems with healthy ageing. During eupnoea, one study has shown relatively higher crural diaphragm electromyographic activity (EMG) in healthy older adults (>51 years) than in younger adults, but these measures may be affected by the normalisation process used. A more direct method to assess neural drive involves the measurement of discharge properties of motor units. Here, to assess age-related changes in neural drive to the diaphragm during eupnoea, EMG was recorded from the costal diaphragm using a monopolar needle electrode in participants from three age groups (n ≥ 7 each): older (65-80 years); middle-aged (43-55 years) and young (23-26 years). In each group, 154, 174 and 110 single motor units were discriminated, respectively. A mixed-effects linear model showed no significant differences between age groups for onset (group mean range 9.5-10.2 Hz), peak (14.1-15.0 Hz) or offset (7.8-8.5 Hz) discharge frequencies during eupnoea. The motor unit recruitment was delayed in the older group (by ∼15% of inspiratory time; p = 0.02 cf. middle-aged group) and had an earlier offset time (by ∼15% of inspiratory time; p = 0.04 cf. young group). However, the onset of multiunit activity was similar across groups, consistent with no global increase in neural drive to the diaphragm with ageing. The area of diaphragm motor unit potentials was ∼40% larger in the middle-aged and older groups (P < 0.02), which indicates axonal sprouting and re-innervation of muscle fibres associated with ageing, even in middle-aged participants.

Single-crystal diamond refractive lens for focusing X-rays in two dimensions. Erratum.

A correction is made to a citation in the article by Antipov et al. (2016) [J. Synchrotron Rad. 23, 163-168].

Single-crystal diamond refractive lens for focusing X-rays in two dimensions.

The fabrication and performance evaluation of single-crystal diamond refractive X-ray lenses of which the surfaces are paraboloids of revolution for focusing X-rays in two dimensions simultaneously are reported. The lenses were manufactured using a femtosecond laser micromachining process and tested using X-ray synchrotron radiation. Such lenses were stacked together to form a standard compound refractive lens (CRL). Owing to the superior physical properties of the material, diamond CRLs could become indispensable wavefront-preserving primary focusing optics for X-ray free-electron lasers and the next-generation synchrotron storage rings. They can be used for highly efficient refocusing of the extremely bright X-ray sources for secondary optical schemes with limited aperture such as nanofocusing Fresnel zone plates and multilayer Laue lenses.

Linkage haplotype for allotypic variants of porcine IgA and IgG subclass genes.

Six putative subclasses of expressed porcine IgG have been described from gene sequences and allotypic variants for five of these have been proposed. We tested this hypothesis by studying the transcription of these 11 variants in outbred hemizygous farm pigs. Since Cγ subclass genes are closely linked, they are most likely inherited as a haplotype. Since hemizygous pigs can only express genes encoded on one chromosome, identifying the expressed genes can indicate which allelic variants are linked as well as testing whether the putative alleles are indeed alleles or separate subclass genes. The procedure for producing B cell knockout pigs has recently been described; our study examines transcripts from the hemizygous parents and offspring generated by this technology. More than 570 Cγ gene clones from hemizygous animals were identified according to subclass and allotype by a combination of clone hybridization and sequencing. IgG3 accounted for 80% in newborn animals but <5% in adults. IgG1 accounted for ~50% of all clones recovered from adults and IgG4 was the least frequently recovered (4%). Results indicate that IgG1(b), IgG2(a), IgG3, IgG4(a), IgG5(a), and IgG6(a) are linked and also linked to IgA(a). This comprises a haplotype for domesticated swine. For simplicity, we propose that the current nomenclature for the allotypes of IgG1 be reversed so that all genes in the Cγ(a)-Cα(a) haplotype are designated "a".

Cathodoluminescence of natural, plastically deformed pink diamonds.

The 49 type I natural pink diamonds examined exhibit color restricted to lamellae or bands oriented along {111} that are created by plastic deformation. Pink diamonds fall into two groups: (1) diamonds from Argyle in Australia and Santa Elena in Venezuela are heavily strained throughout and exhibit pink bands alternating with colorless areas, and (2) diamonds from other localities have strain localized near the discrete pink lamellae. Growth zones are highlighted by a blue cathodoluminescence (CL) and crosscut by the pink lamellae that emit yellowish-green CL that originates from the H3 center. This center probably forms by the recombination of nitrogen-related centers (A-aggregates) and vacancies mobilized by natural annealing in the Earth's mantle. Twinning is the most likely mechanism through which plastic deformation is accommodated for the two groups of diamonds. The plastic deformation creates new centers visible through spectroscopic methods, including the one responsible for the pink color, which remains unidentified. The differences in the plastic deformation features, and resulting CL properties, for the two groups might correlate to the particular geologic conditions under which the diamonds formed; those from Argyle and Santa Elena are deposits located within Proterozoic cratons, whereas most diamonds originate from Archean cratons.

Physiological responses and perceived comfort to high-flow nasal cannula therapy in awake adults: effects of flow magnitude and temperature.

Clinical use of heated, high-flow nasal cannula (HFNC) for noninvasive respiratory support is increasing and may have a therapeutic role in stabilizing the upper airway in obstructive sleep apnea (OSA). However, physiological mechanisms by which HFNC therapy may improve upper airway function and effects of different temperature modes are unclear. Accordingly, this study aimed to determine effects of incremental flows and temperature modes (heated and nonheated) of HFNC on upper airway muscle activity (genioglossus), pharyngeal airway pressure, breathing parameters, and perceived comfort. Six participants (2 females, aged 35 ± 14 yr) were studied during wakefulness in the supine position and received HFNC at variable flows (0-60 L/min) during heated (37°C) and nonheated (21°C) modes. Breathing parameters via calibrated Respitrace inductance bands (chest and abdomen), upper airway pressures via airway transducers, and genioglossus muscle activity via intramuscular bipolar fine wire electrodes were measured. Comfort levels during HFNC were quantified using a visual analog scale. Increasing HFNC flows did not increase genioglossus muscle activation despite increased negative epiglottic pressure swings (P = 0.009). HFNC provided ∼7 cmH2O positive airway pressure at 60 L/min in nonheated and heated modes. In addition, increasing the magnitude of HFNC flow reduced breathing frequency (P = 0.045), increased expiratory time (P = 0.040), increased peak inspiratory flow (P = 0.002), and increased discomfort (P = 0.004). Greater discomfort occurred at higher flows in the nonheated versus the heated mode (P = 0.034). These findings provide novel insight into key physiological changes that occur with HFNC for respiratory support and indicate that the primary mechanism for improved upper airway stability is positive airway pressure, not increased pharyngeal muscle activity.NEW & NOTEWORTHY This study evaluated upper airway muscle function, breathing, and comfort across different HFNC flows and temperatures. There were no increases in genioglossus muscle activity at higher flows despite greater negative epiglottic pressure swings. Increasing negative pressure swings was associated with increasing discomfort in the nonheated mode. HFNC was associated with ∼7 cmH2O increase in positive airway pressure, which may be the primary mechanism for upper airway stability with HFNC rather than increases in pharyngeal muscle activity.

Substantia nigra echomorphology and motor cortex excitability.

The aim of our study was to investigate the relation between substantia nigra (SN) echomorphology and indices of motor cortex excitability. Nigral hyperechogenicity in healthy individuals is thought to represent an SN abnormality or predisposition to Parkinson's disease (PD) and its prevalence is greater in the very old. Our study involved 20 old healthy subjects (aged 72-84 years) known to have normal (n=10) or abnormal (n=10) SN echomorphology. All were in good health with no overt neurological signs. SN morphology was assessed with transcranial sonography through the pre-auricular bone window. Motor cortical excitability and intracortical inhibition were assessed with transcranial magnetic stimulation (TMS) over the first dorsal interosseus motor area. Single stimuli were delivered during relaxation and voluntary contraction and paired stimuli were delivered during relaxation. Each cortical hemisphere was analysed separately. The response to single-pulse TMS (in motor cortex ipsilateral to the target SN) did not differ between groups. However, a significant difference between groups was observed in the paired pulse paradigm (conditioning stimulus intensity: 70% resting motor threshold; interstimulus interval: 2 ms). The conditioned motor evoked potential amplitude was significantly larger ipsilateral to the hyperechogenic SN than in controls (P=0.014). Thus, healthy subjects with SN hyperechogenicity exhibit significantly less intracortical inhibition within the motor cortex than subjects with normal echomorphology. Decreased intracortical inhibition is also observed in PD patients. This study provides further evidence that SN hyperechogenicity in healthy individuals is associated with changes characteristic of PD supporting a role for this feature as a vulnerability marker or state marker for subtle nigral dopaminergic dysfunction.

Differential activation of the human costal and crural diaphragm during voluntary and involuntary breaths.

The diaphragm is the primary muscle that generates the negative intrathoracic pressure to drive inspiratory airflow. The diaphragm consists of two parts, the costal and crural portions, with different roles during inspiration in animals, particularly when the stimulus to breathe is increased. In this study, the neural drive to the costal and crural portions of the diaphragm was assessed in nine healthy participants [8 male, aged 32 ± 13 yr (mean ± SD)]. Inspiratory electromyographic activity (EMG) was recorded from the costal diaphragm by using an intramuscular electrode and from the crural diaphragm with a multipair gastroesophageal catheter. Participants performed voluntary augmented breaths at 120%, 140%, and 160% of their tidal volume and also underwent progressive hypercapnia to induce involuntary breathing. Irrespective of the task, the increase in crural activity (normalized to quiet breathing) was only ~60% of the increase in costal activity (slope: 0.56 ± 0.30, P < 0.001). The onset and peak timing of EMG activity was similar for the costal and crural diaphragm during quiet breathing. Thus, when stimulated by either a voluntary or involuntary drive to breathe above tidal volume, the neural drive to the diaphragm was greater to the costal than to the crural portion.NEW & NOTEWORTHY Simultaneous electromyographic recordings from the human costal and crural diaphragm during voluntary augmented breathing and involuntary rebreathing show that the increase in inspiratory crural diaphragm activity was ~60% of the increase in costal diaphragm activity. However costal to crural diaphragm activation did not differ between the two tasks. The dissociation in the amplitude of activation of the costal and crural diaphragm becomes apparent only as the drive to breathe increases above tidal breathing.

The occupied electronic structure of ultrathin boron doped diamond.

Using angle-resolved photoelectron spectroscopy, we compare the electronic band structure of an ultrathin (1.8 nm) δ-layer of boron-doped diamond with a bulk-like boron doped diamond film (3 µm). Surprisingly, the measurements indicate that except for a small change in the effective mass, there is no significant difference between the electronic structure of these samples, irrespective of their physical dimensionality, except for a small modification of the effective mass. While this suggests that, at the current time, it is not possible to fabricate boron-doped diamond structures with quantum properties, it also means that nanoscale boron doped diamond structures can be fabricated which retain the classical electronic properties of bulk-doped diamond, without a need to consider the influence of quantum confinement.

Porcine IgG: structure, genetics, and evolution.

Eleven genomic porcine Cgamma gene sequences are described that represent six putative subclasses that appear to have originated by gene duplication and exon shuffle. The genes previously described as encoding porcine IgG1 and IgG3 were shown to be the IgG1(a) and IgG1(b) allelic variants of the IGHG1 gene, IgG2a and IgG2b are allelic variants of the IGHG2 gene, while "new" IgG3 is monomorphic, has an extended hinge, is structurally unique, and appears to encode the most evolutionarily conserved porcine IgG. IgG5(b) differs most from its putative allele, and its C(H)1 domain shares sequence homology with the C(H)1 of IgG3. Four animals were identified that lacked either IgG4 or IgG6. Alternative splice variants were also recovered, some lacking the C(H)1 domain and potentially encoding heavy chain only antibodies. Potentially, swine can transcribe >20 different Cgamma chains. A comparison of mammalian Cgamma gene sequences revealed that IgG diversified into subclasses after speciation. Thus, the effector functions for the IgG subclasses of each species should not be extrapolated from "same name subclasses" in other species. Sequence analysis identified motifs likely to interact with Fcgamma receptors, FcRn, protein A, protein G, and C1q. These revealed IgG3 to be most likely to activate complement and bind FcgammaRs. All except IgG5(a) and IgG6(a) should bind to FcgammaRs, while all except IgG6(a) and the putative IgG5 subclass proteins should bind well to porcine FcRn, protein A, and protein G.

The piglet as a model for B cell and immune system development.

The ability to identify factors responsible for disease in all species depends on the ability to separate those factors which are environmental from those that are intrinsic. This is particularly important for studies on the development of the adaptive immune response of neonates. Studies on laboratory rodents or primates have been ambiguous because neither the effect of environmental nor maternal factors on the newborn can be controlled in mammals that: (i) transmit potential maternal immunoregulatory factors in utero and (ii) are altricial and cannot be reared after birth without their mothers. Employing the newborn piglet model can address each of these concerns. However, it comes at the price of having first to characterize the immune system of swine and its development. This review focuses on the porcine B cell system, especially on the methods used for its characterization in fetal studies and neonatal piglets. Understanding these procedures is important in the interpretation of the data obtained. Studies on neonatal piglets have (a) provided valuable information on the development of the adaptive immune system, (b) lead to important advances in evolutionary biology, (c) aided our understanding of passive immunity and (d) provided opportunities to use swine to address specific issues in veterinary and biomedical research and immunotherapy. This review summarizes the history of the development of the piglet as a model for antibody repertoire development, thus providing a framework to guide future investigators.

Abdominal Functional Electrical Stimulation to Augment Respiratory Function in Spinal Cord Injury.

Background: Functional electrical stimulation (FES) is the application of electrical pulses to a nerve to achieve a functional muscle contraction. Surface electrical stimulation of the nerves that innervate the abdominal muscles, termed abdominal FES, can cause the abdominal muscles to contract, even when paralysed after spinal cord injury. As the abdominal muscles are the major expiratory muscles, and commonly partially or completely paralysed in tetraplegia, abdominal FES offers a promising method of improving respiratory function for this patient group. Objective: The aim of the article is to provide readers with a better understanding of how abdominal FES can be used to improve the health of the spinal cord-injured population. Methods: A narrative review of the abdominal FES literature was performed. Results: Abdominal FES can achieve an immediate effective cough in patients with tetraplegia, while the repeated application over 6 weeks of abdominal FES can improve unassisted respiratory function. Ventilator duration and tracheostomy cannulation time can also be reduced with repeated abdominal FES. Conclusion: Abdominal FES is a noninvasive method to achieve functional improvements in cough and respiratory function in acute and chronically injured people with tetraplegia. Potential practical outcomes of this include reduced ventilation duration, assisted tracheostomy decannulation, and a reduction in respiratory complications. All of these outcomes can contribute to reduced morbidity and mortality, improved quality of life, and significant potential cost savings for local health care providers.

Movement of the tongue during normal breathing in awake healthy humans.

Electromyographic (EMG) activity of the airway muscles suggest that genioglossus is the primary upper airway dilator muscle. However, EMG data do not necessarily translate into tissue motion and most imaging modalities are limited to assessment of the surfaces of the upper airway. In this study, we hypothesized that genioglossus moves rhythmically during the respiratory cycle and that the motion within is inhomogeneous. A 'tagged' magnetic resonance imaging technique was used to characterize respiratory-related tissue motions around the human upper airway in quiet breathing. Motion of airway tissues at different segments of the eupnoeic respiratory cycle was imaged in six adult subjects by triggering the scanner at the end of inspiration. Displacements of the 'tags' were analysed using the harmonic phase method (HARP). Respiratory timing was monitored by a band around the upper abdomen. The genioglossus moved during the respiratory cycle. During expiration, the genioglossus moved posteriorly and during inspiration, it moved anteriorly. The degree of motion varied between subjects. The maximal anteroposterior movement of a point tracked on the genioglossus was 1.02 +/- 0.54 mm (mean +/- s.d.). The genioglossus moved over the geniohyoid muscle, with minimal movement in other muscles surrounding the airway at the level of the soft palate. Local deformation of the tongue was analysed using two-dimensional strain maps. Across the respiratory cycle, positive strains within genioglossus reached peaks of 17.5 +/- 9.3% and negative strains reached peaks of -16.3 +/- 9.3% relative to end inspiration. The patterns of strains were consistent with elongation and compression within a constant volume structure. Hence, these data suggest that even during respiration, the tongue behaves as a muscular hydrostat.

The isolator piglet: a model for studying the development of adaptive immunity.

The period from late gestation to weaning in neonatal mammals is a critical window when the adaptive immune system develops and replaces the protection temporarily provided by passive immunity and pre-adaptive antibodies. It is also when oral tolerance to dietary antigen and the distinction between commensal and pathogenic gut bacteria becomes established resulting in immune homeostasis. The reproductive biology of swine provides a unique model for distinguishing the effects of different factors on immune development during this critical period because all extrinsic factors are controlled by the experimenter. This chapter reviews this early stage of development and the usefulness of the piglet model for understanding events during this transitional stage. The review also describes the major features of the porcine immune system and the immune stimulatory and dysregulatory factors that act during this period. The value of the model to medical science in such areas as food allergy, organ transplantation, cystic fibrosis and the production of humanized antibodies for immuno-therapy is discussed.

Antibody Repertoire Development in Swine.

We describe the domestication of the species, explore its value to agriculture and bioscience, and compare its immunoglobulin (Ig) genes to those of other vertebrates. For encyclopedic information, we cite earlier reviews and chapters. We provide current gene maps for the heavy and light chain loci and describe their polygeny and polymorphy. B-cell and antibody repertoire development is a major focus, and we present findings that challenge several mouse-centric paradigms. We focus special attention on the role of ileal Peyer's patches, the largest secondary lymphoid tissues in newborn piglets and a feature of all artiodactyls. We believe swine fetal development and early class switch evolved to provide natural secretory IgA antibodies able to prevent translocation of bacteria from the gut while the bacterial PAMPs drive development of adaptive immunity. We discuss the value of using the isolator piglet model to address these issues.

Optical bleaching, TSL and OSL features of CVD diamond.

Luminescence and optical features of chemical vapour deposition (CVD) diamond have been studied in view of the potential application of this material in ionising radiation dosimetry field. For this purpose, thermally stimulated luminescence (TSL) and optically stimulated luminescence (OSL) techniques have been used. A large amount of work has emphasised the excellent dosimetric properties of CVD diamond. Nevertheless, TSL measurements showed that after irradiation, this material is extremely sensitive to ambient light and the stored dose information is drastically affected by optical bleaching. From OSL analysis, it follows that both types of processes (TSL and OSL) were characterised by the same excitation and emission spectra and that optical bleaching originated from a broad stimulation band lying from visible to near infrared with a continuous character.

Thermoluminescence properties of CVD diamond for clinical dosimetry use.

The application of diamond to dosimetry is desirable because of its tissue equivalence, chemical inertness and small size, but this has not been commercially viable owing to the non-reproducible response of natural diamond. The chemical vapour deposition (CVD) of diamond permits controlled, reproducible and large-scale production of this material at potentially low cost. An investigation of some clinically relevant features like the depth-dose distribution as well as the absorbed dose profile, obtained using thermoluminescence (TL), is reported for several CVD diamond films. The TL characterisation presented here shows that CVD diamond films should be excellent TL-mode detectors in instances of radiotherapy and in vivo radiation dosimetry.

Physicochemical and immunochemical studies on bovine IgA and glycoprotein-a.

1. Bovine secretory IgA (SIgA) from colostrum (mol. wt. about 410,000) is composed of four alpha-chains (mol. wt. 61,000), four light chains (mol. wt. 23,000) and one molecule of glycoprotein-a (mol. wt. 70,000-86,000). The alpha-chains are antigenically and physicochemically distinct from the heavy chains of IgM, IgG1 and IgG2 while the light chains are identical to those occurring on other bovine immunoglobulins. Glycoprotein-a and bovine free secretory component are identical and the former name should be abolished. Much of this protein is covalently bonded to IgA. 2. The gel filtration behavior of serum IgA suggests it is a dimer. 3. The elution behavior of IgA and SIgA from ion-exchange columns and the solubility characteristic of SIgA in the presence of Zn2+ are similar to those of human and rabbit IgA. 4. The disc electrophoretic behavior of IgA and SIgA are distinct from IgM, dimeric IgG1, 7-S IgG and glycoprotein-a. Dimeric IgG1 (s20,w = 9.5) is abundant in colostrum and is similar in size to SIgA. 5. Bovine IgA shows physicochemical and immunochemical heterogeneity when studied by gel filtration, disc electrophoresis, immunoelectrophoresis and ultracentrifugational analyses. Lacrimal and nasal SIgA possess antigenic determinants absent on colostral SIgA.

The differential enzyme susceptibility of bovine immunoglobulin G1 and immunoglobulin G2 to pepsin and papain.

Purified bovine immunoglobulins IgG1 and IgG2 were subjected to enzymatic degradation with pepsin and papain. Results were monitored using density gradient ultracentrifugation, acrylamide electrophosesis and immunodiffusion employing subclass- and light chain-specific antisera. The results indicated a marked enzymatic susceptibility of IgG1 to digestion with pepsin. This differential susceptibility can also be demonstrated in unfractionated bovine gamma-globulin. No striking differences between the two subclasses were observed during treatment with papain in the presence of cysteine and after 24 h, most IgG1 and IgG2 was degraded to Fc and Fab fragments. The pepsin Fc fragment generated from IgG2 was larger than that generated from IgG1 although the F(ab')2 fragments were simialr in size. These results are consistent with the hypothesis that the Fc region of IgG1 contains multiple cleavage sites for pepsin whereas IgG2 has few. Rabbits immunized with the first elution peak from a 30 h pepsin digest of bovine gamma-globulin fractionated on Sephadex G-150, responded primarily to common gamma-chain and IgG2-specific determinants. Thus, the differential susceptibility of bovine subclasses to pepsin provides a method for stimulating IgG2-specific antibodies in rabbits.