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Journal of Sports Science & Medicine Jun 2022Easy-to-use and accurate heart rate variability (HRV) assessments are essential in athletes' follow-up, but artifacts may lead to erroneous analysis. Artifact detection...
Easy-to-use and accurate heart rate variability (HRV) assessments are essential in athletes' follow-up, but artifacts may lead to erroneous analysis. Artifact detection and correction are the purpose of extensive literature and implemented in dedicated analysis programs. However, the effects of number and/or magnitude of artifacts on various time- or frequency-domain parameters remain unclear. The purpose of this study was to assess the effects of artifacts on HRV parameters. Root mean square of the successive differences (RMSSD), standard deviation of the normal to normal inter beat intervals (SDNN), power in the low- (LF) and high-frequency band (HF) were computed from two 4-min RR recordings in 178 participants in both supine and standing positions, respectively. RRs were modified by (1) randomly adding or subtracting 10, 30, 50 or 100 ms to the successive RRs; (2) a single artifact was manually inserted; (3) artifacts were automatically corrected from signal naturally containing artifacts. Finally, RR recordings were analyzed before and after automatic detection-correction of artifacts. Modifying each RR by 10, 30, 50 and 100 ms randomly did not significantly change HRV parameters (range -6%, +6%, supine). In contrast, by adding a single artifact, RMSSD increased by 413% and 269%, SDNN by 54% and 47% in supine and standing positions, respectively. LF and HF changed only between -3% and +8% (supine and standing) in the artifact condition. When more than 0.9% of the signal contained artifacts, RMSSD was significantly biased, whilst when more than 1.4% of the signal contained artifacts LF and HF were significantly biased. RMSSD and SDNN were more sensitive to a single artifact than LF and HF. This indicates that, when using RMSSD only, a single artifact may induce erroneous interpretation of HRV. Therefore, we recommend using both time- and frequency-domain parameters to minimize the errors in the diagnoses of health status or fatigue in athletes.
Topics: Artifacts; Athletes; Heart Rate; Humans; Standing Position
PubMed: 35719238
DOI: 10.52082/jssm.2022.260 -
Journal of Clinical Medicine May 2022There is growing evidence that periodic limb movements in sleep (PLMS) may lead to increased blood pressure (BP) values during the night. The aim of this study was to...
There is growing evidence that periodic limb movements in sleep (PLMS) may lead to increased blood pressure (BP) values during the night. The aim of this study was to assess if patients with disordered sleep and an increased number of PLMS have higher BP values at night. We analyzed 100 polysomnographic (PSG) recordings of patients with disordered sleep, with the exclusion of sleep-related breathing disorders. Patients also registered beat-to-beat blood pressure during PSG. We compared the BP of patients with an increased number of PLMS (more than 5 PLMS per hour of sleep) during the night (examined group, = 50) to the BP of patients with a PLMS number within the normal range (up to 5 PLMS per hour of sleep) (control group, = 50). Patients from the examined group had significantly higher values of systolic BP during the night (119.7 mmHg vs. 113.3 mmHg, = 0.04), sleep (119.0 mmHg vs. 113.3 mmHg, = 0.04), and wake (122.5 mmHg vs. 117.2 mmHg, = 0.04) periods and of diastolic BP during the night (75.5 mmHg vs. 70.6 mmHg, = 0.04) and wake (77.6 mmHg vs. 71.5 mmHg, = 0.01) periods. Our results suggest a relationship between the number of PLMS during the night and the values of nocturnal blood pressure. It is possible that their treatment could lower nocturnal BP in patients with sleep disorders, therefore improving their vascular risk profile.
PubMed: 35628954
DOI: 10.3390/jcm11102829 -
Scientific Reports Jan 2021Cyclophosphamide (CP) is an anticancer drug, an alkylating agent. Cardiotoxicity of CP is associated with one of its metabolites, acrolein, and clinical cardiotoxicity...
Cyclophosphamide (CP) is an anticancer drug, an alkylating agent. Cardiotoxicity of CP is associated with one of its metabolites, acrolein, and clinical cardiotoxicity manifestations are described for cases of taking CP in high doses. Nevertheless, modern arrhythmogenicity prediction assays in vitro include evaluation of beat rhythm and rate as well as suppression of cardiac late markers after acute exposure to CP, but not its metabolites. The mechanism of CP side effects when taken at low doses (i.e., < 100 mg/kg), especially at the cellular level, remains unclear. In this study conduction properties and cytoskeleton structure of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) obtained from a healthy donor under CP were evaluated. Arrhythmogenicity testing including characterization of 3 values: conduction velocity, maximum capture rate (MCR) measurements and number of occasions of re-entry on a standard linear obstacle was conducted and revealed MCR decrease of 25% ± 7% under CP. Also, conductivity area reduced by 34 ± 15%. No effect of CP on voltage-gated ion channels was found. Conduction changes (MCR and conductivity area decrease) are caused by exposure time-dependent alpha-actinin disruption detected both in hiPSC-CMs and neonatal ventricular cardiomyocytes in vitro. Deviation from the external stimulus frequency and appearance of non-conductive areas in cardiac tissue under CP is potentially arrhythmogenic and could develop arrhythmic effects in vivo.
Topics: Action Potentials; Cyclophosphamide; Fibroblasts; Heart Rate; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Patch-Clamp Techniques; Stem Cells
PubMed: 33504826
DOI: 10.1038/s41598-020-79085-5 -
Biophysical Journal Nov 2022The sinoatrial node (SAN) is a complex structure that spontaneously depolarizes rhythmically ("pacing") and excites the surrounding non-automatic cardiac cells ("drive")...
The sinoatrial node (SAN) is a complex structure that spontaneously depolarizes rhythmically ("pacing") and excites the surrounding non-automatic cardiac cells ("drive") to initiate each heart beat. However, the mechanisms by which the SAN cells can activate the large and hyperpolarized surrounding cardiac tissue are incompletely understood. Experimental studies demonstrated the presence of an insulating border that separates the SAN from the hyperpolarizing influence of the surrounding myocardium, except at a discrete number of sinoatrial exit pathways (SEPs). We propose a highly detailed 3D model of the human SAN, including 3D SEPs to study the requirements for successful electrical activation of the primary pacemaking structure of the human heart. A total of 788 simulations investigate the ability of the SAN to pace and drive with different heterogeneous characteristics of the nodal tissue (gradient and mosaic models) and myocyte orientation. A sigmoidal distribution of the tissue conductivity combined with a mosaic model of SAN and atrial cells in the SEP was able to drive the right atrium (RA) at varying rates induced by gradual If block. Additionally, we investigated the influence of the SEPs by varying their number, length, and width. SEPs created a transition zone of transmembrane voltage and ionic currents to enable successful pace and drive. Unsuccessful simulations showed a hyperpolarized transmembrane voltage (-66 mV), which blocked the L-type channels and attenuated the sodium-calcium exchanger. The fiber direction influenced the SEPs that preferentially activated the crista terminalis (CT). The location of the leading pacemaker site (LPS) shifted toward the SEP-free areas. LPSs were located closer to the SEP-free areas (3.46 ± 1.42 mm), where the hyperpolarizing influence of the CT was reduced, compared with a larger distance from the LPS to the areas where SEPs were located (7.17± 0.98 mm). This study identified the geometrical and electrophysiological aspects of the 3D SAN-SEP-CT structure required for successful pace and drive in silico.
Topics: Humans; Sinoatrial Node; Lipopolysaccharides; Action Potentials; Heart Atria; Sodium-Calcium Exchanger
PubMed: 36262044
DOI: 10.1016/j.bpj.2022.10.020 -
Developmental Biology May 2020FgfrL1 is a novel growth factor receptor that is primarily expressed in musculoskeletal tissues and the kidney. FgfrL1-deficient mice have a malformed diaphragm and no...
FgfrL1 is a novel growth factor receptor that is primarily expressed in musculoskeletal tissues and the kidney. FgfrL1-deficient mice have a malformed diaphragm and no kidneys. Such animals die immediately after birth because they are not able to inflate their lungs. The FgfrL1 molecule is composed of three extracellular Ig domains, a transmembrane helix and a short intracellular domain. To investigate the contribution of each of these domains to the function of the novel receptor, we generated mice with deletions of the individual domains. Mice lacking the intracellular domain are viable and phenotypically normal. Mice lacking the first (N-terminal) Ig domain are also viable and normal, but have a reduced life span. Mice lacking the Ig2 or the Ig3 domain are born alive, but die within 24 h after birth. Ig2-deficient animals exhibit substantially smaller kidneys than wild-type littermates and contain a lower number of glomeruli. Ig3-deficient mice completely lack metanephric kidneys. Interestingly, both the Ig2 and the Ig3-deficient animals show only minor alterations in the diaphragm, which still enables them to inflate their lungs after birth. Our results demonstrate that the principal function of the FgfrL1 receptor is to control the growth of the metanephric kidneys by regulating nephrogenesis. It appears that this function is primarily accomplished by the Ig3 domain with some contribution of the Ig2 domain. It is conceivable that the two domains interact with an Fgf ligand and another molecule from the surface of neighboring cells to induce condensation of the metanephric mesenchyme to renal epithelia and glomeruli.
Topics: Animals; Diaphragm; Kidney; Mice; Mice, Inbred C57BL; Mice, Knockout; Musculoskeletal System; Organogenesis; Protein Domains; Receptor, Fibroblast Growth Factor, Type 5
PubMed: 31923383
DOI: 10.1016/j.ydbio.2020.01.003 -
Proceedings of the National Academy of... Dec 2023Idiopathic normal pressure hydrocephalus (iNPH) is an enigmatic neurological disorder that develops after age 60 and is characterized by gait difficulty, dementia, and...
Idiopathic normal pressure hydrocephalus (iNPH) is an enigmatic neurological disorder that develops after age 60 and is characterized by gait difficulty, dementia, and incontinence. Recently, we reported that heterozygous deletions may cause iNPH. Here, we identify mutations affecting nine additional genes (, ) that are statistically enriched among iNPH patients. The encoded proteins are all highly expressed in choroid plexus and ependymal cells, and most have been associated with cilia. Damaging mutations in , which encodes an adenylate kinase, were detected in 9.6% of iNPH patients. Mice homozygous for an iNPH-associated mutation displayed normal cilia structure and number, but decreased cilia motility and beat frequency, communicating hydrocephalus, and balance impairment. +/- mice displayed normal brain development and behavior until early adulthood, but subsequently developed communicating hydrocephalus. Together, our findings suggest that heterozygous mutations that impair ventricular epithelial function may contribute to iNPH.
Topics: Humans; Mice; Animals; Adult; Middle Aged; Hydrocephalus, Normal Pressure; Hydrocephalus; Brain; Choroid Plexus; Mutation; Proteins
PubMed: 38100419
DOI: 10.1073/pnas.2300681120 -
Diagnostic Microbiology and Infectious... Oct 2020On 1 June 2020, 6 million cases of COVID-19 were recorded with a total of 374,927 deaths worldwide. Brazil, at that point, presented a total of 514,992 cases and 29,341... (Review)
Review
On 1 June 2020, 6 million cases of COVID-19 were recorded with a total of 374,927 deaths worldwide. Brazil, at that point, presented a total of 514,992 cases and 29,341 deaths caused by the COVID-19 disease. At that moment, Brazil appeared in the second position regarding number of cases, fourth in number of deaths, second in number of recovered patients (N = 206,555), second in number of follow-up cases (N = 279,096), third in number of active and serious cases (N = 8,318), 39 in number of cases per million inhabitants (N = 2,424), and 125 in number of SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) exams per million inhabitants (N = 4,378). To beat the pandemic, Brazil needs to optimize the COVID-19 diagnosis through the SARS-CoV-2 identification using RT-PCR tests and adjust its policies to save lives. Brazil is in a crucial moment to minimize the impact of the illness on society by reducing the number of new cases and thus, preventing deaths, mainly of the risk group populations. However, as widely announced, in Brazil the diagnosis using RT-PCR is still scarce and part of the material collected from COVID-19 patients was disposed of and many patients were not tested, regardless of the seriousness of the symptoms, due to errors of medical data records, improper conservation of the samples after collection and/or during transport, which compromised the quality of the material to be tested. Moreover, the federal government has supported the end of the quarantine, while the number of deaths has grown in thousands every day and the cases have been expanding to the interior of the country.
Topics: Brazil; COVID-19; COVID-19 Testing; COVID-19 Vaccines; Cause of Death; Clinical Laboratory Techniques; Coronavirus Infections; DNA, Viral; Disease Outbreaks; Female; Global Health; Humans; Male; Pandemics; Pneumonia, Viral; Prevalence; Real-Time Polymerase Chain Reaction; Survival Analysis
PubMed: 32682217
DOI: 10.1016/j.diagmicrobio.2020.115113 -
Frontiers in Aging 2022The process of aging strongly correlates with maladaptive architectural, mechanical, and biochemical alterations that contribute to the decline in cardiac function.... (Review)
Review
The process of aging strongly correlates with maladaptive architectural, mechanical, and biochemical alterations that contribute to the decline in cardiac function. Consequently, aging is a major risk factor for the development of heart disease, the leading cause of death in the developed world. In this review, we will summarize the classic and recently uncovered pathological changes within the aged heart with an emphasis on the mitochondria. Specifically, we describe the metabolic changes that occur in the aging heart as well as the loss of mitochondrial fitness and function and how these factors contribute to the decline in cardiomyocyte number. In addition, we highlight recent pharmacological, genetic, or behavioral therapeutic intervention advancements that may alleviate age-related cardiac decline.
PubMed: 35958271
DOI: 10.3389/fragi.2022.951417 -
The New Phytologist Apr 2021The glycoalkaloid saponin α-tomatine is a tomato-specific secondary metabolite that accumulates to millimolar levels in vegetative tissues and has antimicrobial and...
The glycoalkaloid saponin α-tomatine is a tomato-specific secondary metabolite that accumulates to millimolar levels in vegetative tissues and has antimicrobial and antinutritional activity that kills microbial pathogens and deters herbivorous insects. We describe recent insights into the biosynthetic pathway of α-tomatine synthesis and its regulation. We discuss the mode of action of α-tomatine by physically interacting with sterols, thereby disrupting membranes, and how tomato protects itself from its toxic action. Tomato pathogenic microbes can enzymatically hydrolyze, and thereby inactivate, α-tomatine using either of three distinct types of glycosyl hydrolases. We also describe findings that extend well beyond the simple concept of plants producing toxins and pathogens inactivating them. There are reports that toxicity of α-tomatine is modulated by external pH, that α-tomatine can trigger programmed cell death in fungi, that cellular localization matters for the impact of α-tomatine on invading microbes, and that α-tomatine breakdown products generated by microbial hydrolytic enzymes can modulate plant immune responses. Finally, we address a number of outstanding questions that deserve attention in the future.
Topics: Solanum lycopersicum; Saponins; Sterols; Taste; Tomatine
PubMed: 33220068
DOI: 10.1111/nph.17104 -
Scientific Reports Mar 2021Respiratory mucociliary clearance (MCC) is a key defense mechanism that functions to entrap and transport inhaled pollutants, particulates, and pathogens away from the...
Respiratory mucociliary clearance (MCC) is a key defense mechanism that functions to entrap and transport inhaled pollutants, particulates, and pathogens away from the lungs. Previous work has identified a number of anesthetics to have cilia depressive effects in vitro. Wild-type C57BL/6 J mice received intra-tracheal installation of Tc-Sulfur colloid, and were imaged using a dual-modality SPECT/CT system at 0 and 6 h to measure baseline MCC (n = 8). Mice were challenged for one hour with inhalational 1.5% isoflurane, or intraperitoneal ketamine (100 mg/kg)/xylazine (20 mg/kg), ketamine (0.5 mg/kg)/dexmedetomidine (50 mg/kg), fentanyl (0.2 mg/kg)/1.5% isoflurane, propofol (120 mg/Kg), or fentanyl/midazolam/dexmedetomidine (0.025 mg/kg/2.5 mg/kg/0.25 mg/kg) prior to MCC assessment. The baseline MCC was 6.4%, and was significantly reduced to 3.7% (p = 0.04) and 3.0% (p = 0.01) by ketamine/xylazine and ketamine/dexmedetomidine challenge respectively. Importantly, combinations of drugs containing fentanyl, and propofol in isolation did not significantly depress MCC. Although no change in cilia length or percent ciliation was expected, we tried to correlate ex-vivo tracheal cilia ciliary beat frequency and cilia-generated flow velocities with MCC and found no correlation. Our results indicate that anesthetics containing ketamine (ketamine/xylazine and ketamine/dexmedetomidine) significantly depress MCC, while combinations containing fentanyl (fentanyl/isoflurane, fentanyl/midazolam/dexmedetomidine) and propofol do not. Our method for assessing MCC is reproducible and has utility for studying the effects of other drug combinations.
Topics: Anesthetics, Inhalation; Animals; Drug Combinations; Mice; Mice, Inbred C57BL; Mucociliary Clearance
PubMed: 33649513
DOI: 10.1038/s41598-021-84605-y