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Increasingly prevalent, nontuberculous mycobacteria (NTM) infections affect approximately 20% of people with cystic fibrosis (CF). Previous studies of CF sputum identified lower levels of the host metabolite itaconate in those infected with NTM. Itaconate can inhibit the growth of M. tuberculosis (MTB) in vitro via the inhibition of the glyoxylate cycle enzyme (ICL), but its impact on NTM is unclear. To test itaconic acid's (IA) effect on NTM growth, laboratory and CF clinical strains of Mycobacterium abscessus and Mycobacterium avium were cultured in 7H9 minimal media supplemented with 1-10 mM of IA and short-chain fatty acids (SCFA). M. avium and M. abscessus grew when supplemented with SCFAs, whereas the addition of IA (≥ 10 mM) completely inhibited NTM growth. NTM supplemented with acetate or propionate and 5 mM IA displayed slower growth than NTM cultured with SCFA and ≤ 1 mM of IA. However, IA's inhibition of NTM was pH dependent; as similar and higher quantities (100 mM) of pH adjusted IA (pH 7) did not inhibit growth in vitro, while in an acidic minimal media (pH 6.1), 1 to 5 mM of non-pH adjusted IA inhibited growth. None of the examined isolates displayed the ability to utilize IA as a carbon source, and IA added to M. abscessus isocitrate lyase (ICL) decreased enzymatic activity. Lastly, the addition of cell-permeable 4-octyl itaconate (4-OI) to THP-1 cells enhanced NTM clearance, demonstrating a potential role for IA/itaconate in host defense against NTM infections.
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Succinatos , Succinatos/farmacologia , Succinatos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Micobactérias não Tuberculosas/efeitos dos fármacos , Micobactérias não Tuberculosas/crescimento & desenvolvimento , Células THP-1 , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium avium/efeitos dos fármacos , Mycobacterium avium/crescimento & desenvolvimento , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/crescimento & desenvolvimento , Mycobacterium abscessus/metabolismoRESUMO
Peripheral vascular diseases (PVDs) represent a significant burden on global human health and healthcare systems. With continued growth in obesity and diabetes, it is likely that the incidence of these conditions will increase. As many PVDs remain undiagnosed, low-cost and easy to use diagnostic methods are required. This work uses newly developed wearable electro-resistive morphic sensors to assess venous and arterial competence in the lower limbs of 36 healthy subjects. Comparison of this HeMo device was made to currently available benchtop light reflection rheography and photoplethymography devices. Results indicate that HeMo can detect the physiological signals of interest for both chronic venous insufficiency and peripheral arterial disease and all subjects were interpreted as healthy by each system. However, measurement repeatability of HeMo was highlighted as an issue that requires further system development. Furthermore, as HeMo captures changes in a section of limb circumference due to changes in underlying blood movement, rather than at a single point, the recorded signal is typically damped by comparison. This factor should be considered in any future developments.
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Doença Arterial Periférica , Insuficiência Venosa , Dispositivos Eletrônicos Vestíveis , Humanos , Insuficiência Venosa/diagnóstico , Veias , Extremidade Inferior , Doença Arterial Periférica/diagnósticoRESUMO
Transcranial doppler (TCD) ultrasound probes are an invaluable tool in cerebral blood flow (CBF) studies. Their operation demands maintaining consistent pose on the subject throughout the experimental protocol. However, the displacement of the TCD probe during vestibular studies is common and substantially prolongs the experiment or even terminates it. This is a significant challenge for integrating motion-based vestibular studies with CBF investigations. In response, a mechatronics system is designed to allow remote repositioning of the TCD probe during data collection experiments while the subject is wearing a head mounted virtual reality (VR) display and seated in a vestibular disorientation device. This paper presents the design, prototype, and operation of this mechatronics apparatus.Clinical Relevance- The mechatronics apparatus of this paper can enable motion-based vestibular studies that entail the use of CBF velocity measurement and head-mounted virtual reality display.
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Vestíbulo do Labirinto , Realidade Virtual , Ultrassonografia Doppler Transcraniana/métodos , Circulação Cerebrovascular/fisiologia , Vestíbulo do Labirinto/diagnóstico por imagem , Movimento (Física)RESUMO
Effective monitoring of respiratory disturbances during sleep requires a sensor capable of accurately capturing chest movements or airflow displacement. Gold-standard monitoring of sleep and breathing through polysomnography achieves this task through dedicated chest/abdomen bands, thermistors, and nasal flow sensors, and more detailed physiology, evaluations via a nasal mask, pneumotachograph, and airway pressure sensors. However, these measurement approaches can be invasive and time-consuming to perform and analyze. This work compares the performance of a non-invasive wearable stretchable morphic sensor, which does not require direct skin contact, embedded in a t-shirt worn by 32 volunteer participants (26 males, 6 females) with sleep-disordered breathing who performed a detailed, overnight in-laboratory sleep study. Direct comparison of computed respiratory parameters from morphic sensors versus traditional polysomnography had approximately 95% (95 ± 0.7) accuracy. These findings confirm that novel wearable morphic sensors provide a viable alternative to non-invasively and simultaneously capture respiratory rate and chest and abdominal motions.
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Taxa Respiratória , Síndromes da Apneia do Sono , Masculino , Feminino , Humanos , Polissonografia , Sono/fisiologia , Síndromes da Apneia do Sono/diagnóstico , RespiraçãoRESUMO
Heart rate (HR) and respiratory rate (RR) are two vital parameters of the body medically used for diagnosing short/long-term illness. Out-of-the-body, non-skin-contact HR/RR measurement remains a challenge due to imprecise readings. "Invisible" wearables integrated into day-to-day garments have the potential to produce precise readings with a comfortable user experience. Sleep studies and patient monitoring benefit from "Invisibles" due to longer wearability without significant discomfort. This paper suggests a novel method to reduce the footprint of sleep monitoring devices. We use a single silver-coated nylon fabric band integrated into a substrate of a standard cotton/nylon garment as a resistive elastomer sensor to measure air and blood volume change across the chest. We introduce a novel event-based architecture to process data at the edge device and describe two algorithms to calculate real-time HR/RR on ARM Cortex-M3 and Cortex-M4F microcontrollers. RR estimations show a sensitivity of 99.03% and a precision of 99.03% for identifying individual respiratory peaks. The two algorithms used for HR calculation show a mean absolute error of 0.81 ± 0.97 and 0.86±0.61 beats/min compared with a gold standard ECG-based HR. The event-based algorithm converts the respiratory/pulse waveform into instantaneous events, therefore reducing the data size by 40-140 times and requiring 33% less power to process and transfer data. Furthermore, we show that events hold enough information to reconstruct the original waveform, retaining pulse and respiratory activity. We suggest fabric sensors and event-based algorithms would drastically reduce the device footprint and increase the performance for HR/RR estimations during sleep studies, providing a better user experience.
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Nylons , Taxa Respiratória , Frequência Cardíaca/fisiologia , Humanos , Polissonografia , Taxa Respiratória/fisiologia , SonoRESUMO
BACKGROUND: An anticipated surge in mental health service demand related to COVID-19 has motivated the use of novel methods of care to meet demand, given workforce limitations. Digital health technologies in the form of self-tracking technology have been identified as a potential avenue, provided sufficient evidence exists to support their effectiveness in mental health contexts. OBJECTIVE: This literature review aims to identify current and potential physiological or physiologically related monitoring capabilities of the Apple Watch relevant to mental health monitoring and examine the accuracy and validation status of these measures and their implications for mental health treatment. METHODS: A literature review was conducted from June 2021 to July 2021 of both published and gray literature pertaining to the Apple Watch, mental health, and physiology. The literature review identified studies validating the sensor capabilities of the Apple Watch. RESULTS: A total of 5583 paper titles were identified, with 115 (2.06%) reviewed in full. Of these 115 papers, 19 (16.5%) were related to Apple Watch validation or comparison studies. Most studies showed that the Apple Watch could measure heart rate acceptably with increased errors in case of movement. Accurate energy expenditure measurements are difficult for most wearables, with the Apple Watch generally providing the best results compared with peers, despite overestimation. Heart rate variability measurements were found to have gaps in data but were able to detect mild mental stress. Activity monitoring with step counting showed good agreement, although wheelchair use was found to be prone to overestimation and poor performance on overground tasks. Atrial fibrillation detection showed mixed results, in part because of a high inconclusive result rate, but may be useful for ongoing monitoring. No studies recorded validation of the Sleep app feature; however, accelerometer-based sleep monitoring showed high accuracy and sensitivity in detecting sleep. CONCLUSIONS: The results are encouraging regarding the application of the Apple Watch in mental health, particularly as heart rate variability is a key indicator of changes in both physical and emotional states. Particular benefits may be derived through avoidance of recall bias and collection of supporting ecological context data. However, a lack of methodologically robust and replicated evidence of user benefit, a supportive health economic analysis, and concerns about personal health information remain key factors that must be addressed to enable broader uptake.
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Nontuberculous mycobacterial (NTM) pulmonary infections in people with cystic fibrosis (CF) are associated with significant morbidity and mortality and are increasing in prevalence. Host risk factors for NTM infection in CF are largely unknown. We hypothesize that the airway microbiota represents a host risk factor for NTM infection. In this study, 69 sputum samples were collected from 59 people with CF; 42 samples from 32 subjects with NTM infection (14 samples collected before incident NTM infection and 28 samples collected following incident NTM infection) were compared to 27 samples from 27 subjects without NTM infection. Sputum samples were analyzed with 16S rRNA gene sequencing and metabolomics. A supervised classification and correlation analysis framework (sparse partial least-squares discriminant analysis [sPLS-DA]) was used to identify correlations between the microbial and metabolomic profiles of the NTM cases compared to the NTM-negative controls. Several metabolites significantly differed in the NTM cases compared to controls, including decreased levels of tryptophan-associated and branched-chain amino acid metabolites, while compounds involved in phospholipid metabolism displayed increased levels. When the metabolome and microbiome data were integrated by sPLS-DA, the models and component ordinations showed separation between the NTM and control samples. While this study could not determine if the observed differences in sputum metabolites between the cohorts reflect metabolic changes that occurred as a result of the NTM infection or metabolic features that contributed to NTM acquisition, it is hypothesis generating for future work to investigate host and bacterial community factors that may contribute to NTM infection risk in CF. IMPORTANCE Host risk factors for nontuberculous mycobacterial (NTM) infection in people with cystic fibrosis (CF) are largely unclear. The goal of this study was to help identify potential host and bacterial community risk factors for NTM infection in people with CF, using microbiome and metabolome data from CF sputum samples. The data obtained in this study identified several metabolic profile differences in sputum associated with NTM infection in CF, including 2-methylcitrate/homocitrate and selected ceramides. These findings represent potential risk factors and therapeutic targets for preventing and/or treating NTM infections in people with CF.
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Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Infecções Oportunistas , Bactérias , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Humanos , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas , RNA Ribossômico 16S/genética , Escarro/microbiologiaRESUMO
Galvanic vestibular stimulation (GVS) has been shown to improve vestibular function potentially via stochastic resonance, however, it remains unknown how central vestibular nuclei process these signals. In vivo work applying electrical stimuli to the vestibular apparatus of animals has shown changes in neuronal discharge at the level of the primary vestibular afferents and hair cells. This study aimed to determine the cellular impacts of stochastic, sinusoidal, and stochastic + sinusoidal stimuli on individual medial vestibular nucleus (MVN) neurons of male and female C57BL/6 mice. All stimuli increased the irregularity of MVN neuronal discharge, while differentially affecting neuronal gain. This suggests that the heterogeneous MVN neuronal population (marked by differential expression of ion channels), may influence the impact of electrical stimuli on neuronal discharge. Neuronal subtypes showed increased variability of neuronal firing, where Type A and B neurons experienced the largest gain changes in response to stochastic and sinusoidal stimuli. Type C neurons were the least affected regarding neuronal firing variability and gain changes. The membrane potential (MP) of neurons was altered by sinusoidal and stochastic + sinusoidal stimuli, with Type B and C neuronal MP significantly affected. These results indicate that GVS-like electrical stimuli impact MVN neuronal discharge differentially, likely as a result of heterogeneous ion channel expression.
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Neurônios , Núcleos Vestibulares , Animais , Feminino , Masculino , Potenciais da Membrana , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologiaRESUMO
Zebrafish (Danio rerio) are an attractive model organism for a variety of scientific studies, including host-microbe interactions. The organism is particularly useful for the study of aquatic microbes that can colonize vertebrate hosts, including Vibrio cholerae, an intestinal pathogen. V. cholerae must colonize the intestine of an exposed host for pathogenicity to occur. While numerous studies have explored various aspects of the pathogenic effects of V. cholerae on zebrafish and other model organisms, few, if any, have examined how a V. cholerae infection alters the resident intestinal microbiome and the role of the type six secretion system (T6SS) in that process. In this study, 16S rRNA gene sequencing was utilized to investigate how strains of V. cholerae both with and without the T6SS alter the aforementioned microbial profiles following an infection. V. cholerae infection induced significant changes in the zebrafish intestinal microbiome, and while not necessary for colonization, the T6SS was important for inducing mucin secretion, a marker for diarrhea. Additional salient differences to the microbiome were observed based on the presence or absence of the T6SS in the V. cholerae utilized for challenging the zebrafish hosts. We conclude that V. cholerae significantly modulates the zebrafish intestinal microbiome to enable colonization and that the T6SS is important for pathogenesis induced by the examined V. cholerae strains. Furthermore, the presence or absence of T6SS differentially and significantly affected the composition and structure of the intestinal microbiome, with an increased abundance of other Vibrio bacteria observed in the absence of V. cholerae T6SS.
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Cólera/microbiologia , Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos , Interações Hospedeiro-Patógeno , Sistemas de Secreção Tipo VI/fisiologia , Vibrio cholerae/fisiologia , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Metagenômica/métodos , RNA Ribossômico 16S , Peixe-ZebraRESUMO
Zebrafish (Danio rerio) is an attractive model organism to use for an array of scientific studies, including host-microbe interactions. Zebrafish contain a core (i.e., consistently detected) intestinal microbiome consisting primarily of Proteobacteria. Furthermore, this core intestinal microbiome is plastic and can be significantly altered due to external factors. Zebrafish are particularly useful for the study of aquatic microbes that can colonize vertebrate hosts, including Vibrio cholerae. As an intestinal pathogen, V. cholerae must colonize the intestine of an exposed host for pathogenicity to occur. Members of the resident intestinal microbial community likely must be reduced or eliminated by V. cholerae for colonization, and subsequent disease, to occur. Many studies have explored a variety of aspects of the pathogenic effects of V. cholerae on zebrafish and other model organisms but few have researched how a V. cholerae infection changes the resident intestinal microbiome. In this study, 16S rRNA gene sequencing was used to examine how five genetically diverse V. cholerae strains alter the intestinal microbiome following an infection. We found that V. cholerae colonization induced significant changes in the zebrafish intestinal microbiome. Notably, changes in the microbial profile were significantly different from each other, based on the particular strain of V. cholerae used to infect zebrafish hosts. We conclude that V. cholerae significantly modulates the zebrafish intestinal microbiota to enable colonization and that specific microbes that are targeted depend on the V. cholerae genotype.
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Cólera/microbiologia , Suscetibilidade a Doenças , Microbioma Gastrointestinal , Interações Hospedeiro-Patógeno , Interações Microbianas , Vibrio cholerae/fisiologia , Animais , Modelos Animais de Doenças , Metagenômica/métodos , RNA Ribossômico 16S , Peixe-ZebraRESUMO
Background: Wearable technologies are increasingly popular. Yet their use remains low by older adults, who may stand the greatest benefit of use. While there is an abundance of research examining the performance, accuracy, specificity, and sensitivity of wearable devices, many barriers remain and need to be addressed to optimize uptake in clinical practice. There is a paucity of research exploring factors that help to understand barriers and facilitators to inform acceptance, adoption, wearability, and sustainability of use. Objectives: (1) To explore the perceptions and experiences of older adults and health professionals about using wearable cardiac monitoring technologies, and (2) to identify barriers and facilitators of acceptance and uptake of these devices in clinical practice. Methods: A systematic review with a qualitative meta-synthesis was undertaken. Results: A total of 7 original research studies were included.Four interrelated themes emerged: (1) trust, including safety, and confidence; (2) functionality and affordability; (3) risks; and (4) assurance. Conclusion: There are many barriers and facilitators to the adoption of wearable devices based on experiences of older adults, health professionals, and carers. Most significant factors related to the design aspects of the devices, appropriate and timely feedback, user-friendly technology, and issues related to affordability and cost.
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BACKGROUND: New wearable devices (for example, AliveCor or Zio patch) offer promise in detecting arrhythmia and monitoring cardiac health status, among other clinically useful parameters in older adults. However, the clinical utility and usability from the perspectives of clinicians is largely unexplored. OBJECTIVE: This study aimed to explore clinician perspectives on the use of wearable cardiac monitoring technology for older adults. METHODS: A descriptive qualitative study was conducted using semistructured focus group interviews. Clinicians were recruited through purposive sampling of physicians, nurses, and allied health staff working in 3 tertiary-level hospitals. Verbatim transcripts were analyzed using thematic content analysis to identify themes. RESULTS: Clinicians representing physicians, nurses, and allied health staff working in 3 tertiary-level hospitals completed 4 focus group interviews between May 2019 and July 2019. There were 50 participants (28 men and 22 women), including cardiologists, geriatricians, nurses, and allied health staff. The focus groups generated the following 3 overarching, interrelated themes: (1) the current state of play, understanding the perceived challenges of patient cardiac monitoring in hospitals, (2) priorities in cardiac monitoring, what parameters new technologies should measure, and (3) cardiac monitoring of the future, "the ideal device." CONCLUSIONS: There remain pitfalls related to the design of wearable cardiac technology for older adults that present clinical challenges. These pitfalls and challenges likely negatively impact the uptake of wearable cardiac monitoring in routine clinical care. Partnering with clinicians and patients in the co-design of new wearable cardiac monitoring technologies is critical to optimize the use of these devices and their uptake in clinical care.
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The comfortable, continuous monitoring of vital parameters is still a challenge. The long-term measurement of respiration and cardiovascular signals is required to diagnose cardiovascular and respiratory diseases. Similarly, sleep quality assessment and the recovery period following acute treatments require long-term vital parameter datalogging. To address these requirements, we have developed "VitalCore", a wearable continuous vital parameter monitoring device in the form of a T-shirt targeting the uninterrupted monitoring of respiration, pulse, and actigraphy. VitalCore uses polymer-based stretchable resistive bands as the primary sensor to capture breathing and pulse patterns from chest expansion. The carbon black-impregnated polymer is implemented in a U-shaped configuration and attached to the T-shirt with "interfacing" material along with the accompanying electronics. In this paper, VitalCore is bench tested and compared to gold standard respiration and pulse measurements to verify its functionality and further to assess the quality of data captured during sleep and during light exercise (walking). We show that these polymer-based sensors could identify respiratory peaks with a sensitivity of 99.44%, precision of 96.23%, and false-negative rate of 0.557% during sleep. We also show that this T-shirt configuration allows the wearer to sleep in all sleeping positions with a negligible difference of data quality. The device was also able to capture breathing during gait with 88.9%-100% accuracy in respiratory peak detection.
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Elastômeros/química , Eletrocardiografia/métodos , Sono/fisiologia , Fuligem/química , Eletrocardiografia/instrumentação , Frequência Cardíaca , Humanos , Taxa Respiratória , Caminhada , Dispositivos Eletrônicos VestíveisRESUMO
INTRODUCTION: The effects of resistance exercise on vascular function are unclear. AIM: To investigate the acute haemodynamic (blood pressure and augmentation index) and rate of perceived exertion (RPE) response to two types of resistance exercises of equal workload-a set of unilateral 35% of one repetition maximum (1RM) quadriceps extension and a set of unilateral 70% 1RM quadriceps extension. METHODS: Twenty two young healthy males completed both exercises on separate days. Heart rate, central and peripheral systolic and diastolic blood pressure (BP), augmentation pressure, augmentation index (AIx), augmentation index at a heart rate of 75 beats per minute (AIx75), and RPE were measured using applanation tonometry before exercise, immediately after exercise, 5 min after exercise and 15 min after exercise. RESULTS: AIx75 was significantly lower 5 min after exercising at 35% of 1RM than 70% of 1RM. Systolic blood pressure was significantly lower at 5 min post exercise for both intensities. There was no significant difference in RPE between conditions or time points. CONCLUSIONS: Results suggest that changes in blood pressure and augmentation index vary depending on the intensity of resistance exercise regardless of the volume of exercise carried out. Changes in AIx75 in response to resistance exercise may be independent of changes in BP.
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Pressão Sanguínea , Contração Muscular , Músculo Quadríceps/fisiologia , Treinamento Resistido/métodos , Adolescente , Adulto , Estudos Cross-Over , Voluntários Saudáveis , Frequência Cardíaca , Humanos , Masculino , Projetos Piloto , Distribuição Aleatória , Fatores de Tempo , Adulto JovemRESUMO
Stretchable conductive materials are originally conceived as radio frequency (RF) and electromagnetic interference (EMI) shielding materials, and, under stretch, they generally function as distributed strain-gauges. These commercially available conductive elastomers have found their space in low power health monitoring systems, for example, to monitor respiratory and cardiac functions. Conductive elastomers do not behave linearly due to material constraints; hence, when used as a sensor, a full characterisation to identify ideal operating ranges are required. In this paper, we studied how the continuous stretch cycles affected the material electrical and physical properties in different embodiment impressed by bodily volume change. We simulated the stretch associated with breathing using a bespoke stress rig to ensure reproducibility of results. The stretch rig is capable of providing constant sinusoidal waves in the physiological ranges of extension and frequency. The material performances is evaluated assessing the total harmonic distortion (THD), signal-to-noise ratio (SNR), correlation coefficient, peak to peak (P-P) amplitude, accuracy, repeatability, hysteresis, delay, and washability. The results showed that, among the three controlled variables, stretch length, stretch frequency and fabric width, the most significant factor to the signal quality is the stretch length. The ideal working region is within 2% of the original length. The material cut in strips of > 3 show more reliable to handle a variety of stretch parameter without losing its internal characteristics and electrical properties.
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Monitorização Fisiológica/métodos , Condutividade Elétrica , Processamento Eletrônico de Dados , Monitorização Fisiológica/instrumentação , Reprodutibilidade dos Testes , Razão Sinal-RuídoRESUMO
Galvanic vestibular stimulation (GVS) has been shown to improve balance measures in individuals with balance or vestibular impairments. This is proposed to be due to the stochastic resonance (SR) phenomenon, which is defined as application of a low-level/subthreshold stimulus to a non-linear system to increase detection of weaker signals. However, it is still unknown how SR exhibits its positive effects on human balance. This is one of the first demonstrations of the effects of sinusoidal and stochastic noise on individual neurons. Using whole-cell patch clamp electrophysiology, sinusoidal and stochastic noise can be applied directly to individual neurons in the medial vestibular nucleus (MVN) of C57BL/6 mice. Here we demonstrate how to determine the threshold of MVN neurons in order to ensure the sinusoidal and stochastic stimuli are subthreshold and from this, determine the effects that each type of noise has on MVN neuronal gain. We show that subthreshold sinusoidal and stochastic noise can modulate the sensitivity of individual neurons in the MVN without affecting basal firing rates.
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Neurônios/fisiologia , Núcleos Vestibulares/fisiologia , Potenciais de Ação/fisiologia , Animais , Camundongos Endogâmicos C57BL , Processos EstocásticosRESUMO
Groundtruth is a Matlab Graphical User Interface (GUI) developed for the identification of key features and artifacts within physiological signals. The ultimate aim of this GUI is to provide a simple means of assessing the performance of new sensors. Secondary, to this is providing a means of providing marked data, enabling assessment of automated artifact rejection and feature identification algorithms. With the emergence of new wearable sensor technologies, there is an unmet need for convenient assessment of device performance, and a faster means of assessing new algorithms. The proposed GUI allows interactive marking of artifact regions as well as simultaneous interactive identification of key features, e.g., respiration peaks in respiration signals, R-peaks in Electrocardiography signals, etc. In this paper, we present the base structure of the system, together with an example of its use for two simultaneously worn respiration sensors. The respiration rates are computed for both original as well as artifact removed data and validated using Bland-Altman plots. The respiration rates computed based on the proposed GUI (after artifact removal process) demonstrated consistent results for two respiration sensors after artifact removal process. Groundtruth is customizable, and alternative processing modules are easy to add/remove. Groundtruth is intended for open-source use.
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Klebsiella pneumoniae (Kp), one of the most common causes of healthcare-associated infections, increases patient morbidity, mortality, and hospitalization costs. Kp must acquire nutrients from the host for successful infection; however, the host is able to prevent bacterial nutrient acquisition through multiple systems. This includes the innate immune protein lipocalin 2 (Lcn2), which prevents Kp iron acquisition. To identify novel Lcn2-dependent Kp factors that mediate evasion of nutritional immunity during lung infection, we undertook an InSeq study using a pool of >20,000 transposon mutants administered to Lcn2+/+ and Lcn2-/- mice. Comparing transposon mutant frequencies between mouse genotypes, we identified the Kp citrate synthase, GltA, as potentially interacting with Lcn2, and this novel finding was independently validated. Interestingly, in vitro studies suggest that this interaction is not direct. Given that GltA is involved in oxidative metabolism, we screened the ability of this mutant to use a variety of carbon and nitrogen sources. The results indicated that the gltA mutant has a distinct amino acid auxotrophy rendering it reliant upon glutamate family amino acids for growth. Deletion of Lcn2 from the host leads to increased amino acid levels in bronchioloalveolar lavage fluid, corresponding to increased fitness of the gltA mutant in vivo and ex vivo. Accordingly, addition of glutamate family amino acids to Lcn2+/+ bronchioloalveolar lavage fluid rescued growth of the gltA mutant. Using a variety of mouse models of infection, we show that GltA is an organ-specific fitness factor required for complete fitness in the spleen, liver, and gut, but dispensable in the bloodstream. Similar to bronchioloalveolar lavage fluid, addition of glutamate family amino acids to Lcn2+/+ organ lysates was sufficient to rescue the loss of gltA. Together, this study describes a critical role for GltA in Kp infection and provides unique insight into how metabolic flexibility impacts bacterial fitness during infection.
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Citrato (si)-Sintase/metabolismo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/crescimento & desenvolvimento , Lipocalina-2/metabolismo , Lipocalina-2/fisiologia , Animais , Citrato (si)-Sintase/genética , Modelos Animais de Doenças , Humanos , Infecções por Klebsiella/metabolismo , Klebsiella pneumoniae/enzimologia , Lipocalina-2/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
An original wireless stimulator for peripheral nerves based on a metal loop (diameter ≈1 mm) that is powered by a transcranial magnetic stimulator (TMS) and does not require circuitry components is reported. The loop can be integrated in a chitosan scaffold that functions as a graft when applied onto transected nerves (graft-antenna). The graft-antenna is bonded to rat sciatic nerves by a laser without sutures; it does not migrate after implantation and is able to trigger steady compound muscle action potentials for 12 weeks (CMAP ≈1.3 mV). Eight weeks postoperatively, axon regeneration is facilitated in transected nerves that are repaired with the graft-antenna and stimulated by the TMS for 1 h per week. The graft-antenna is an innovative and minimally-invasive device that functions concurrently as a wireless stimulator and adhesive scaffold for nerve repair.