Reflex response to airway occlusion in human inspiratory muscles when recruited for breathing and posture

Briefly occluding the airway during inspiration produces a short-latency reflex inhibition in human inspiratory muscles. This occlusion reflex seems specific to respiratory muscles; however, it is not known whether the reflex inhibition has a uniform effect across a motoneuron pool when a muscle is recruited concurrently for breathing and posture. In this study, participants were seated and breathed through a mouthpiece that occluded inspiratory airflow for 250 ms at a volume threshold of 0.2 liters. The reflex response was measured in the scalene and sternocleidomastoid muscles during 1) a control condition with the head supported in space and the muscles recruited for breathing only, 2) a postural condition with the head unsupported and the neck flexors recruited for both breathing and to maintain head posture, and 3) a large-breath condition with the head supported and the volume threshold raised to between 0.8 and 1.0 liters to increase inspiratory muscle activity. When normalized to its preocclusion mean, the reflex response in the scalene muscles was not significantly different between the large-breath and control conditions, whereas concomitant recruitment of these muscles for posture control reduced the reflex response by half compared with the control condition. A reflex response occurred in sternocleidomastoid when it contracted phasically as an accessory muscle for inspiration during the large-breath condition. These results indicate that the occlusion reflex does not produce a uniform effect across the motoneuron pool and that afferent inputs for this reflex most likely act via intersegmental networks of premotoneurons rather than at a motoneuronal level

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

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

Tongue acceleration in humans evoked with intramuscular electrical stimulation of genioglossus

Genioglossus was stimulated intramuscularly to determine the effect of regional activation of the muscle on tongue movement in eight healthy adults. Stimulation at motor threshold was delivered with a needle electrode inserted to different depths in the anterior and posterior regions of genioglossus. The current amplitude that induced muscle contraction was ∼80% higher for anterior than posterior sites. Evoked tongue movements were determined from stimulus-triggered averages (150 pulses) of the outputs from an accelerometer fixed to the posterosuperior surface of the tongue. The median amplitude [95% confidence intervals] for the resultant acceleration was 0.0 m/s2 [0.0, 0.2] for anterior and 0.6 m/s2 [0.1, 2.8] for posterior sites. There was a positive relationship between acceleration amplitude and stimulation depth in the posterior of genioglossus (p < 0.001), but acceleration amplitude did not vary with stimulation depth in the anterior region (p = 0.83). This heterogeneity in acceleration responses between muscle regions may contribute to differences in collapsibility of the upper airway

Genioglossus motor unit activity in supine and upright postures in obstructive sleep apnea

This study investigated whether a change in posture affected the activity of the upper-airway dilator muscle genioglossus in participants with and without obstructive sleep apnea (OSA). During wakefulness, a monopolar needle electrode was used to record single motor unit activity in genioglossus in supine and upright positions to alter the gravitational load that causes narrowing of the upper airway. Activity from 472 motor units was recorded during quiet breathing in 17 males, nine of whom had OSA. The mean number of motor units for each participant was 11.8 (SD 3.4) in the upright and 16.0 (SD 4.2) in the supine posture. For respiratory-modulated motor units, there were no significant differences in discharge frequencies between healthy controls and participants with OSA. Within each breath, genioglossus activity increased through the recruitment of phasic motor units and an increase in firing rate, with an overall increase of ∼6 Hz (50%) across both postures and participant groups. However, the supine posture did not lead to compensatory increases in the peak discharge frequencies of inspiratory and expiratory motor units, despite the increase in gravitational load on the upper airway. Posture also had no significant effect on the discharge frequency of motor units that showed no respiratory modulation during quiet breathing. We postulate that, in wakefulness, any increase in genioglossus activity to compensate for the gravitational effects on the upper airway is achieved primarily through the recruitment of additional motor units in both healthy controls and participants with OSA

Bacterial Pathogens and Symbionts Harboured by Ixodes ricinus Ticks Parasitising Red Squirrels in the United Kingdom

Red squirrels (Sciurus vulgaris) are native to most of Eurasia; in much of the United Kingdom, they have been supplanted by the non-native grey squirrel, and are considered an endangered species. Very little is known about the range of tick-borne pathogens to which UK red squirrels are exposed. As part of trap-and-release surveys examining prevalence of Mycobacterium spp. in red squirrel populations on two UK islands, Ixodes ricinus ticks were removed from squirrels and PCR screened for Borrelia spp., intracellular arthropod-borne bacteria and the parasitic wasp Ixodiphagus hookeri. At both sites, the most commonly encountered tick-transmitted bacterium was Borrelia burgdorferi sensu lato (overall minimum prevalence 12.7%), followed by Anaplasma phagocytophilum (overall minimum prevalence 1.6%). Single ticks infected with Spiroplasma were found at both sites, and single ticks infected with Borrelia miyamotoi or an Ehrlichia sp. at one site. Ticks harbouring Wolbachia (overall minimum prevalence 15.2%) were all positive for I. hookeri. Our study shows that UK red squirrels are potentially exposed to a variety of bacterial pathogens via feeding ticks. The effects on the health and survival of this already vulnerable wildlife species are unknown, and further studies are needed to evaluate the threat posed to red squirrels by Borrelia and other tick-borne pathogens

Rings in the Solar System: a short review

Rings are ubiquitous around giant planets in our Solar System. They evolve jointly with the nearby satellite system. They could form either during the giant planet formation process or much later, as a result of large scale dynamical instabilities either in the local satellite system, or at the planetary scale. We review here the main characteristics of rings in our solar system, and discuss their main evolution processes and possible origin. We also discuss the recent discovery of rings around small bodies.Comment: Accepted for the Handbook of Exoplanet

Intergenerational Practice in the Community—What Does the Community Think?

The many changes that occur in the lives of older people put them at an increased risk of being socially isolated and lonely. Intergenerational programs for older adults and young children can potentially address this shortfall, because of the perceived benefit from generations interacting. This study explores whether there is an appetite in the community for intergenerational programs for community dwelling older adults. An online survey was distributed via social media, research team networks, and snowballing recruitment with access provided via QR code or hyperlink. Semi-structured interviews were undertaken with potential participants of a pilot intergenerational program planned for the Eastern Suburbs of Sydney, Australia in 2020. The interviews were thematically analyzed. Over 250 people completed the survey, and 21 interviews took place with older adults (10) and parents of young children (11). The data showed that participants were all in favor of intergenerational programs, but there were different perceptions about who benefits most and how. The study highlighted considerations to be addressed in the development of effective and sustainable intergenerational programs. For example, accessing people in the community who are most socially isolated and lonely was identified as a primary challenge. More evidence-based research is needed to support involvement of different cohorts, such as those who are frail, or living with physical or cognitive limitations.</jats:p

Imagable 4T1 model for the study of late stage breast cancer

<p>Abstract</p> <p>Background</p> <p>The 4T1 mouse mammary tumor cell line is one of only a few breast cancer models with the capacity to metastasize efficiently to sites affected in human breast cancer. Here we describe two 4T1 cell lines modified to facilitate analysis of tumor growth and metastasis and evaluation of gene function <it>in vivo</it>. New information regarding the involvement of innate and acquired immunity in metastasis and other characteristics of the model relevant to its use in the study of late stage breast cancer are reported.</p> <p>Methods</p> <p>The lines were engineered for stable expression of firefly luciferase to allow tracking and quantitation of the cells <it>in vivo</it>. Biophotonic imaging was used to characterize growth and metastasis of the lines <it>in vivo </it>and an improved gene expression approach was used to characterize the basis for the metastatic phenotype that was observed.</p> <p>Results</p> <p>Growth of cells at the primary site was biphasic with metastasis detected during the second growth phase 5–6 weeks after introduction of the cells. Regression of growth, which occurred in weeks 3–4, was associated with extensive necrosis and infiltration of leukocytes. Biphasic tumor growth did not occur in BALB/c SCID mice indicating involvement of an acquired immune response in the effect. Hematopoiesis in spleen and liver and elevated levels of circulating leukocytes were observed at week 2 and increased progressively until death at week 6–8. Gene expression analysis revealed an association of several secreted factors including colony stimulatory factors, cytokines and chemokines, acute phase proteins, angiogenesis factors and ECM modifying proteins with the 4T1 metastatic phenotype. Signaling pathways likely to be responsible for production of these factors were also identified.</p> <p>Conclusion</p> <p>The production of factors that stimulate angiogenesis and ECM modification and induce hematopoiesis, recruitment and activation of leukocytes suggest that 4T1 tumor cells play a more direct role than previously appreciated in orchestrating changes in the tumor environment conducive to tumor cell dissemination and metastasis. The new cell lines will greatly facilitate the study of late stage breast and preclinical assessment of cancer drugs and other therapeutics particularly those targeting immune system effects on tumor metastasis.</p

A new real-time PCR method to overcome significant quantitative inaccuracy due to slight amplification inhibition

<p>Abstract</p> <p>Background</p> <p>Real-time PCR analysis is a sensitive DNA quantification technique that has recently gained considerable attention in biotechnology, microbiology and molecular diagnostics. Although, the cycle-threshold (<it>Ct</it>) method is the present "gold standard", it is far from being a standard assay. Uniform reaction efficiency among samples is the most important assumption of this method. Nevertheless, some authors have reported that it may not be correct and a slight PCR efficiency decrease of about 4% could result in an error of up to 400% using the <it>Ct </it>method. This reaction efficiency decrease may be caused by inhibiting agents used during nucleic acid extraction or copurified from the biological sample.</p> <p>We propose a new method (<it>Cy</it>_<it>0</it>) that does not require the assumption of equal reaction efficiency between unknowns and standard curve.</p> <p>Results</p> <p>The <it>Cy</it>_{<it>0 </it>}method is based on the fit of Richards' equation to real-time PCR data by nonlinear regression in order to obtain the best fit estimators of reaction parameters. Subsequently, these parameters were used to calculate the <it>Cy</it>_{<it>0 </it>}value that minimizes the dependence of its value on PCR kinetic.</p> <p>The <it>Ct</it>, second derivative (<it>Cp</it>), sigmoidal curve fitting method (<it>SCF</it>) and <it>Cy</it>_{<it>0 </it>}methods were compared using two criteria: precision and accuracy. Our results demonstrated that, in optimal amplification conditions, these four methods are equally precise and accurate. However, when PCR efficiency was slightly decreased, diluting amplification mix quantity or adding a biological inhibitor such as IgG, the <it>SCF</it>, <it>Ct </it>and <it>Cp </it>methods were markedly impaired while the <it>Cy</it>_{<it>0 </it>}method gave significantly more accurate and precise results.</p> <p>Conclusion</p> <p>Our results demonstrate that <it>Cy</it>_{<it>0 </it>}represents a significant improvement over the standard methods for obtaining a reliable and precise nucleic acid quantification even in sub-optimal amplification conditions overcoming the underestimation caused by the presence of some PCR inhibitors.</p