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European Journal of Cell Biology Jun 2024Desmin gene mutations cause myopathies and cardiomyopathies. Our previously characterised R349P desminopathy mice, which carry the ortholog of the common human desmin...
Desmin gene mutations cause myopathies and cardiomyopathies. Our previously characterised R349P desminopathy mice, which carry the ortholog of the common human desmin mutation R350P, showed marked alterations in mitochondrial morphology and function in muscle tissue. By isolating skeletal muscle myoblasts from offspring of R349P desminopathy and p53 knock-out mice, we established an immortalised cellular disease model. Heterozygous and homozygous R349P desmin knock-in and wild-type myoblasts could be well differentiated into multinucleated spontaneously contracting myotubes. The desminopathy myoblasts showed the characteristic disruption of the desmin cytoskeleton and desmin protein aggregation, and the desminopathy myotubes showed the characteristic myofibrillar irregularities. Long-term electrical pulse stimulation promoted myotube differentiation and markedly increased their spontaneous contraction rate. In both heterozygous and homozygous R349P desminopathy myotubes, this treatment restored a regular myofibrillar cross-striation pattern as seen in wild-type myotubes. High-resolution respirometry of mitochondria purified from myotubes by density gradient ultracentrifugation revealed normal oxidative phosphorylation capacity, but a significantly reduced proton leak in mitochondria from the homozygous R349P desmin knock-in cells. Consistent with a reduced proton flux across the inner mitochondrial membrane, our quantitative proteomic analysis of the purified mitochondria revealed significantly reduced levels of ADP/ATP translocases in the homozygous R349P desmin knock-in genotype. As this alteration was also detected in the soleus muscle of R349P desminopathy mice, which, in contrast to the mitochondria purified from cultured cells, showed a variety of other dysregulated mitochondrial proteins, we consider this finding to be an early step in the pathogenesis of secondary mitochondriopathy in desminopathy.
Topics: Animals; Desmin; Mice; Muscle Fibers, Skeletal; Gene Knock-In Techniques; Protons; Mitochondria; Muscular Dystrophies; Cardiomyopathies
PubMed: 38412640
DOI: 10.1016/j.ejcb.2024.151399 -
BioRxiv : the Preprint Server For... Feb 2024Regaining sensory feedback is pivotal for people living with limb amputation. Electrical stimulation of sensory fibers in peripheral nerves has been shown to restore...
Regaining sensory feedback is pivotal for people living with limb amputation. Electrical stimulation of sensory fibers in peripheral nerves has been shown to restore focal percepts in the missing limb. However, conventional rectangular current pulses induce sensations often described as unnatural. This is likely due to the synchronous and periodic nature of activity evoked by these pulses. Here we introduce a fast-oscillating amplitude-modulated sinusoidal (FAMS) stimulation waveform that desynchronizes evoked neural activity. We used a computational model to show that sinusoidal waveforms evoke asynchronous and irregular firing and that firing patterns are frequency dependent. We designed the FAMS waveform to leverage both low- and high-frequency effects and found that membrane non-linearities enhance neuron-specific differences when exposed to FAMS. We implemented this waveform in a feline model of peripheral nerve stimulation and demonstrated that FAMS-evoked activity is more asynchronous than activity evoked by rectangular pulses, while being easily controllable with simple stimulation parameters. These results represent an important step towards biomimetic stimulation strategies useful for clinical applications to restore sensory feedback.
PubMed: 38405798
DOI: 10.1101/2024.02.14.580219 -
American Heart Journal May 2024Atrial fibrillation (AF) increases the risk of death, stroke, heart failure, cognitive decline, and healthcare costs but is often asymptomatic and undiagnosed. There is... (Observational Study)
Observational Study
BACKGROUND
Atrial fibrillation (AF) increases the risk of death, stroke, heart failure, cognitive decline, and healthcare costs but is often asymptomatic and undiagnosed. There is currently no national screening program for AF. The advent of validated hand-held devices allows AF to be detected in non-healthcare settings, enabling screening to be undertaken within the community.
METHOD AND RESULTS
In this novel observational study, we embedded a MyDiagnostick single lead ECG sensor into the handles of shopping trolleys in four supermarkets in the Northwest of England: 2155 participants were recruited. Of these, 231 participants either activated the sensor or had an irregular pulse, suggesting AF. Some participants agreed to use the sensor but refused to provide their contact details, or consent to pulse assessment. In addition, some data were missing, resulting in 203 participants being included in the final analyses. Fifty-nine participants (mean age 73.6 years, 43% female) were confirmed or suspected of having AF; 20 were known to have AF and 39 were previously undiagnosed. There was no evidence of AF in 115 participants and the remaining 46 recordings were non-diagnostic, mainly due to artefact. Men and older participants were significantly more likely to have newly diagnosed AF. Due to the number of non-diagnostic ECGs (n = 46), we completed three levels of analyses, excluding all non-diagnostic ECGs, assuming all non-diagnostic ECGs were masking AF, and assuming all non-diagnostic ECGs were not AF. Based on the results of the three analyses, the sensor's sensitivity (95% CI) ranged from 0.70 to 0.93; specificity from 0.15 to 0.97; positive predictive values (PPV) and negative predictive values (NPV) ranged from 0.24 to 0.56 and 0.55 to 1.00, respectively. These values should be interpreted with caution, as the ideal reference standard on 1934 participants was imperfect.
CONCLUSION
The study demonstrates that the public will engage with AF screening undertaken as part of their daily routines using hand-held devices. Sensors can play a key role in identifying asymptomatic patients in this way, but the technology must be further developed to reduce the quantity of non-diagnostic ECGs.
Topics: Humans; Atrial Fibrillation; Male; Female; Feasibility Studies; Aged; Electrocardiography; Mass Screening; England; Middle Aged; Aged, 80 and over
PubMed: 38395294
DOI: 10.1016/j.ahj.2024.02.011 -
ACS Applied Materials & Interfaces Feb 2024Capture and real-time recording of precise body movements using strain sensors provide personal information for healthcare monitoring and management. To acquire this...
Capture and real-time recording of precise body movements using strain sensors provide personal information for healthcare monitoring and management. To acquire this information, a sensor that conforms to curved irregular surfaces, including biological tissue, is desired to record complex body movements while acting like a second skin to avoid interference with the movements. In this study, we developed a thin-film-type capacitive strain sensor that is flexible and stretchable on the surface of a living body. We fabricated conductive polymeric ultrathin films ("nanosheets") comprising polystyrene--polybutadiene (SB) elastomers and single-walled carbon nanotubes (SWCNTs) (i.e., SWCNT-SB nanosheets) via gravure coating; the SWCNT-SB-coated nanosheets were used as the flexible electrode in a capacitive strain sensor. The dielectric (DE) layer was then prepared using the silicone elastomer Ecoflex 00-30 because its Young's modulus is comparable to that of the epidermis. The normalized capacitance changes (Δ/) in the sensor increased with increasing tensile strain over a range from 0-100%, indicating that the proposed sensor can measure the strain of biological movements, including those of skin and blood vessels. To improve sensor conformability further, the effect of sensor thickness on the gauge factor (GF) was investigated using thinner DE layers by focusing on their flexural rigidity. As a result, the GF increased from 0.64 to 1.13 as the DE layer thickness decreased from 260 to 40 μm. Finally, we evaluated the fabricated sensor's signal stability and mechanical durability, including during wireless sensing when applied to human skin and a vascular model. The Δ/ values varied in response to the bending motion of a finger, dilation of a blood vessel, and the swallowing movement of the throat. These results indicate that our capacitive strain sensor is conformable and functional on biological tissue to enable monitoring of dynamic biological movements (e.g., pulse rate and arterial dilation) without wearer discomfort.
Topics: Humans; Wearable Electronic Devices; Nanotubes, Carbon; Elastic Modulus; Movement; Motion
PubMed: 38375854
DOI: 10.1021/acsami.3c19320 -
Pediatric Research Feb 2024Manual tactile stimulation is used to counteract apnea in preterm infants, but it is unknown when this intervention should be applied. We compared an anticipatory to a...
BACKGROUND
Manual tactile stimulation is used to counteract apnea in preterm infants, but it is unknown when this intervention should be applied. We compared an anticipatory to a reactive approach using vibrotactile stimulation to prevent hypoxia induced apneas.
METHODS
Preterm rabbit kittens were prematurely delivered and randomized to either group. All kittens breathed spontaneously with a positive airway pressure of 8 cmHO while they were imaged using phase contrast X-ray. Irregular breathing (IB) was induced using gradual hypoxia. The anticipatory group received stimulation at the onset of IB and the reactive group if IB transitioned into apnea. Breathing rate (BR), heart rate (HR) and functional residual capacity (FRC) were compared.
RESULTS
Anticipatory stimulation significantly reduced apnea incidence and maximum inter-breath intervals and increased BR following IB, compared to reactive stimulation. Recovery in BR but not HR was more likely with anticipatory stimulation, although both BR and HR were significantly higher at 120 s after stimulation onset. FRC values and variability were not different.
CONCLUSIONS
Anticipated vibrotactile stimulation is more effective in preventing apnea and enhancing breathing when compared to reactive stimulation in preterm rabbits. Stimulation timing is likely to be a key factor in reducing the incidence and duration of apnea.
IMPACT
Anticipated vibrotactile stimulation can prevent apnea and stimulate breathing effort in preterm rabbits. Anticipated vibrotactile stimulation increases the likelihood of breathing rate recovery following hypoxia induced irregular breathing, when compared to reactive stimulation. Automated stimulation in combination with predictive algorithms may improve the treatment of apnea in preterm infants.
PubMed: 38356025
DOI: 10.1038/s41390-024-03061-2 -
Applied Spectroscopy Apr 2024Plutonium research has been stifled by the significant number of administrative controls and safety procedures, space and instrumentation limitations in radiological...
Plutonium research has been stifled by the significant number of administrative controls and safety procedures, space and instrumentation limitations in radiological gloveboxes, and the potential for personnel and equipment contamination. To address the limited number of spectroscopic studies in Pu-bearing compounds in the current scientific literature, this work presents the use of double-walled cells (DWCs) in "clean" buildings/laboratories as an alternative to research in radiological gloveboxes. This study reports the first laser-induced breakdown spectroscopy (LIBS) experiments of a PuO pellet contained within a DWC, where the formation of elemental (atomic and ionic) species as well as the evolution from elemental to molecular products (PuO) was measured. Raman spectroscopy was also used to characterize the surface of the ablated pellet and the particulates deposited on the window of the inner cell. The full width half-maximum of the T band enabled us to obtain an estimate of the temperature at the pellet surface after the ablation pulse and the particulates based on the crystal lattice disorder. Particulates deposited on the window of the DWC during laser ablation were characterized using scanning electron microscopy, where molten irregular particulates and spheroids were observed. This exciting research conducted in a DWC describes our initial attempts to incorporate LIBS in the arsenal of spectroscopic tools for nuclear forensics applications.
PubMed: 38317274
DOI: 10.1177/00037028241226977 -
International Journal of Pediatrics 2024Respiratory difficulties are a common concern in preterm infants, and they can lead to long-term health problems. Few studies have investigated the use of spectral...
BACKGROUND
Respiratory difficulties are a common concern in preterm infants, and they can lead to long-term health problems. Few studies have investigated the use of spectral analysis as a biomarker to quantify respiration patterns in preterm infants.
OBJECTIVE
To evaluate the feasibility of using spectral analysis of heart rate variability as a biomarker for the quantification of respiratory patterns in very-low-birth-weight preterm infants compared to direct observation.
METHODS
In a comparative, small-scale feasibility study, 18 preterm infants born during their 27 to 28 gestational week (weighing <1500 grams) participated by convenience. Respiratory patterns (regular or irregular; shallow or deep) were directly observed on the 28 week during playback of speech recording. Heart rate variability was simultaneously measured using spectral analysis of heart periods, from which the mean values influenced by respiratory sinus arrhythmia (frequencies of 0.30-1.0 Hz) were compared to each observed respiratory pattern. The magnitudes of respiratory sinus arrhythmia and the area under the curve were determined.
RESULTS
The magnitude of respiratory sinus arrhythmia (frequencies of 0.30-1.0 Hz) in infants observed to be displaying irregular shallow respiration was greater than that in infants with regular deep respiration. Further, there was a shift from lower frequencies (frequency peak = 0.30 Hz) to higher frequencies (peak = 0.70 Hz).
CONCLUSION
In contrast with direct observation, spectral analysis allowed for the quantification of respiratory patterns in a vulnerable population of preterm infants of interest to the nursing scientific and practice community. Future directions include applying this biomarker to evaluate both developmental and pathological trends in the respiratory patterns of preterm infants.
PubMed: 38314331
DOI: 10.1155/2024/6671906 -
International Journal of Sports... Mar 2024Monitoring player readiness to train and perform is an important practical concept in football. Despite an abundance of research in this area in the male game, to date,...
PURPOSE
Monitoring player readiness to train and perform is an important practical concept in football. Despite an abundance of research in this area in the male game, to date, research is limited in female football. The aims of this study were, first, to summarize the current literature on the monitoring of readiness in female football; second, to summarize the current evidence regarding the monitoring of the menstrual cycle and its potential impact on physical preparation and performance in female footballers; and third, to offer practical recommendations based on the current evidence for practitioners working with female football players.
CONCLUSIONS
Practitioners should include both objective (eg, heart rate and countermovement jump) and subjective measures (eg, athlete-reported outcome measures) in their monitoring practices. This would allow them to have a better picture of female players' readiness. Practitioners should assess the reliability of their monitoring (objective and subjective) tools before adopting them with their players. The use of athlete-reported outcome measures could play a key role in contexts where technology is not available (eg, in semiprofessional and amateur clubs); however, practitioners need to be aware that many single-item athlete-reported outcome measures instruments have not been properly validated. Finally, tracking the menstrual cycle can identify menstrual dysfunction (eg, infrequent or irregular menstruation) that can indicate a state of low energy availability or an underlying gynecological issue, both of which warrant further investigation by medical practitioners.
Topics: Female; Humans; Male; Athletes; Heart Rate; Reproducibility of Results; Soccer
PubMed: 38307011
DOI: 10.1123/ijspp.2023-0405 -
Therapeutic Advances in Drug Safety 2024Atrial fibrillation (AF) and obesity are common conditions globally; yet, there remains suboptimal pharmacological management contributing to high rates of...
BACKGROUND
Atrial fibrillation (AF) and obesity are common conditions globally; yet, there remains suboptimal pharmacological management contributing to high rates of hospitalization in patients with AF. The altered pathophysiology of both obese and underweight individuals may influence the pharmacology of medications, including those used to manage AF. This, in turn, increases the risk of adverse events and impacts patient risk for stroke and rehospitalization. Despite the well-established complications of obesity, research investigating the relationship between obesity and AF is scant.
OBJECTIVES
The primary aim of this study is to describe cardiovascular-related hospitalization in AF patients according to BMI categories. A secondary aim is to describe anticoagulant and antiarrhythmic prescribing practice patterns in patients with AF, according to the BMI category.
DESIGN
A retrospective, exploratory descriptive observational cohort study, using routinely collected electronic medical record data from five public hospitals within a single health district, with a population dominantly that is culturally and linguistically diverse, and has a low socioeconomic status.
METHODS AND ANALYSIS
Data extraction will include a 24-month period (January 2017 to December 2018) with a 12-month follow-up. All adult (⩾18 years) patients at discharge diagnosed with AF, prescribed any oral anticoagulant and/or oral rate/rhythm control agent, will be eligible for inclusion.
ETHICS AND DISSEMINATION
Ethics approval from the health district and the University of Wollongong has been granted. Findings will seek to demonstrate associations between management strategies and patient outcomes, as well as describe patterns of acute care management from prescribers. These data will be used to inform and generate hypotheses for large-scale studies examining the impact of body weight on anticoagulation prescribing at national and global scales.
PubMed: 38300763
DOI: 10.1177/20420986241227014 -
PLOS Digital Health Jan 2024The interplay between circadian rhythms, time awake, and mood remains poorly understood in the real-world. Individuals in high-stress occupations with irregular...
The interplay between circadian rhythms, time awake, and mood remains poorly understood in the real-world. Individuals in high-stress occupations with irregular schedules or nighttime shifts are particularly vulnerable to depression and other mood disorders. Advances in wearable technology have provided the opportunity to study these interactions outside of a controlled laboratory environment. Here, we examine the effects of circadian rhythms and time awake on mood in first-year physicians using wearables. Continuous heart rate, step count, sleep data, and daily mood scores were collected from 2,602 medical interns across 168,311 days of Fitbit data. Circadian time and time awake were extracted from minute-by-minute wearable heart rate and motion measurements. Linear mixed modeling determined the relationship between mood, circadian rhythm, and time awake. In this cohort, mood was modulated by circadian timekeeping (p<0.001). Furthermore, we show that increasing time awake both deteriorates mood (p<0.001) and amplifies mood's circadian rhythm nonlinearly. These findings demonstrate the contributions of both circadian rhythms and sleep deprivation to underlying mood and show how these factors can be studied in real-world settings using Fitbits. They underscore the promising opportunity to harness wearables in deploying chronotherapies for psychiatric illness.
PubMed: 38295082
DOI: 10.1371/journal.pdig.0000439