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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 -
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 -
Pacing and Clinical Electrophysiology :... Apr 2022Hemodynamically optimal atrioventricular (AV) delay can be derived by echocardiography or beat-by-beat blood pressure (BP) measurements, but analysis is labor intensive....
BACKGROUND
Hemodynamically optimal atrioventricular (AV) delay can be derived by echocardiography or beat-by-beat blood pressure (BP) measurements, but analysis is labor intensive. Laser Doppler perfusion monitoring measures blood flow and can be incorporated into future implantable cardiac devices. We assess whether laser Doppler can be used instead of BP to optimize AV delay.
METHODS
Fifty eight patients underwent 94 AV delay optimizations with biventricular or His-bundle pacing using laser Doppler and simultaneous noninvasive beat-by-beat BP. Optimal AV delay was defined using a curve of hemodynamic response to switching from AAI (reference state) to DDD (test state) at several AV delays (40-320 ms), with automatic quality control checking precision of the optimum. Five subsequent patients underwent an extended protocol to test the impact of greater numbers of alternations on optimization quality.
RESULTS
55/94 optimizations passed quality control resulting in an optimal AV delay on laser Doppler similar to that derived by BP (median absolute deviation 12 ms). An extended protocol with increasing number of replicates consistently improved quality and reduced disagreement between laser Doppler and BP optima. With only five replicates, no optimization passed quality control, and the median absolute deviation would be 29 ms. These improved progressively until at 50 replicates, all optimizations passed quality control and the median absolute deviation was only 13 ms.
CONCLUSIONS
Laser Doppler perfusion produces hemodynamic optima equivalent to BP. Quality control can be automatic. Adding more replicates, consistently improves quality. Future implantable devices could use such methods to dynamically and reliably optimize AV delays.
Topics: Atrioventricular Node; Biomarkers; Cardiac Pacing, Artificial; Heart Ventricles; Hemodynamics; Humans; Pacemaker, Artificial
PubMed: 34967945
DOI: 10.1111/pace.14434 -
Bulletin of Emergency and Trauma Apr 2019To find a proper search strategy to do a systematic review related to preparedness for disasters. (Review)
Review
OBJECTIVE
To find a proper search strategy to do a systematic review related to preparedness for disasters.
METHODS
MeSH and Emtree terms were searched to detect synonyms for two main search terms "disaster" and "preparedness". Expert opinion on the synonyms was examined applying a Google form. The adopted syntax was searched in PubMed and results were sifted. Hand searching in two top key journals was done and sensitivity was calculated.
RESULTS
Out of 1120 articles, 122 were included. In PDM journal, 10 articles were included by hand searching, out of which 5 were not spotted in PubMed search with the proposed syntax. In DMPHP journal, 13 publications were included, with 5 not found in PubMed search. Because of human error in hand searching 2 articles were added.
CONCLUSION
The proposed syntax in this study achieves a sensitivity of search of 0.6 in PubMed which could be quite applicable for researchers. Moreover, in case only MeSH or Emtree terms were applied in search strategy or where hand searching was not performed, there were a number of articles missed.
PubMed: 31198795
DOI: 10.29252/beat-070201. -
Proceedings. Biological Sciences Dec 2021Energetic expenditure is an important factor in animal locomotion. Here we test the hypothesis that fishes control tail-beat kinematics to optimize energetic expenditure...
Energetic expenditure is an important factor in animal locomotion. Here we test the hypothesis that fishes control tail-beat kinematics to optimize energetic expenditure during undulatory swimming. We focus on two energetic indices used in swimming hydrodynamics, cost of transport and Froude efficiency. To rule out one index in favour of another, we use computational-fluid dynamics models to compare experimentally observed fish kinematics with predicted performance landscapes and identify energy-optimized kinematics for a carangiform swimmer, an anguilliform swimmer and larval fishes. By locating the areas in the predicted performance landscapes that are occupied by actual fishes, we found that fishes use combinations of tail-beat frequency and amplitude that minimize cost of transport. This energy-optimizing strategy also explains why fishes increase frequency rather than amplitude to swim faster, and why fishes swim within a narrow range of Strouhal numbers. By quantifying how undulatory-wave kinematics affect thrust, drag, and power, we explain why amplitude and frequency are not equivalent in speed control, and why Froude efficiency is not a reliable energetic indicator. These insights may inspire future research in aquatic organisms and bioinspired robotics using undulatory propulsion.
Topics: Animals; Biomechanical Phenomena; Fishes; Hydrodynamics; Models, Biological; Swimming
PubMed: 34847768
DOI: 10.1098/rspb.2021.1601 -
European Review For Medical and... May 2022Winter swimming is a new sport discipline. Very little is known, however, about the sex differences, origin, participation and performance of the world's best winter...
OBJECTIVE
Winter swimming is a new sport discipline. Very little is known, however, about the sex differences, origin, participation and performance of the world's best winter swimmers. Therefore, the study aimed to investigate sex differences in performance and age. Furthermore, it should be determined which country has the fastest swimmers, the highest numbers of participants and the most successful age group athletes in winter swimming.
SUBJECTS AND METHODS
A total of 6,477 results from the 25 m events of the IWSA (International Winter Swimming Association) World Cups from 2016-2020 was collected from the official website of IWSA. Data were analyzed using a generalized linear model (GLM) with a gamma probability distribution and identity link function. The 25 m events were carried out in head-up breaststroke style, freestyle and butterfly. The nationalities were grouped into six groups, the five nationalities with the highest number of participants in the 25 m competitions and one group with the other nationalities. The mean time of 25 m races by sex and country of the total sample was compared. For the top 10 comparisons, the best ten athletes from the six groups were selected. The mean time of each top 10 groups was compared by sex and nationality.
RESULTS
Men were faster than women for all categories. Swimmers in age group 15-29 years were the fastest, where females were the fastest in age group 15-19 years and males in age group 20-29 years. Women from both Russia and Estonia and men from both Russia and China were the fastest. Both Russian and Chinese males were the fastest in all water categories in the top 10 section in the 25 m events.
CONCLUSIONS
In summary, males were faster than females in the IWSA World Cups between 2016 and 2020. The age group of 15-29 years old athletes was the most successful while females had their age of peak performance earlier than males. Russian and Estonian males and Russian females were the overall fastest in the 25 m events in all water categories. Future studies should investigate the optimal anthropometric characteristics of male and female winter swimming sprint athletes and whether there are distinct areas in Russia, Estonia and China, where many international winter swimming athletes originate.
Topics: Adolescent; Adult; Athletes; Athletic Performance; Ethnicity; Female; Humans; Male; Swimming; Water; Young Adult
PubMed: 35647827
DOI: 10.26355/eurrev_202205_28841 -
The Lancet. Rheumatology Jan 2023Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with widespread immune dysregulation and diverse clinical features. Immune abnormalities...
BACKGROUND
Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with widespread immune dysregulation and diverse clinical features. Immune abnormalities might be differentially associated with specific organ involvement or response to targeted therapies. We aimed to identify biomarkers of response to belimumab after rituximab to facilitate a personalised approach to therapy.
METHODS
In this exploratory analysis of a randomised controlled trial (BEAT-LUPUS), we investigated immune profiles of patients with SLE recruited to the 52-week clinical trial, which tested the combination of rituximab plus belimumab versus rituximab plus placebo. We used machine learning and conventional statistics to investigate relevant laboratory and clinical biomarkers associated with major clinical response. BEAT LUPUS is registered at ISRCTN, 47873003, and is now complete.
FINDINGS
Between Feb 2, 2017, and March 28, 2019, 52 patients were recruited to BEAT-LUPUS, of whom 44 provided clinical data at week 52 and were included in this analysis. 21 (48%) of 44 participants were in the belimumab group (mean age 39·5 years [SD 12·1]; 17 [81%] were female, four [19%] were male, 13 [62%] were White) and 23 (52%) were in the placebo group (mean age 42·1 years [SD 10·5]; 21 [91%] were female, two [9%] were male, 16 [70%] were White). Ten (48%) of 21 participants who received belimumab after rituximab and eight (35%) of 23 who received placebo after rituximab had a major clinical response at 52 weeks (between-group difference of 13% [95% CI -15 to 38]). We found a predictive association between baseline serum IgA2 anti-double stranded DNA (dsDNA) antibody concentrations and clinical response to belimumab after rituximab, with a between-group difference in major clinical response of 48% (95% CI 10 to 70) in patients with elevated baseline serum IgA2 anti-dsDNA antibody concentrations. Moreover, among those who had a major clinical response, serum IgA2 anti-dsDNA antibody concentrations significantly decreased from baseline only in the belimumab group. Increased circulating IgA2 (but not total) plasmablast numbers, and T follicular helper cell numbers predicted clinical response and were both reduced only in patients who responded to belimumab after rituximab. Serum IgA2 anti-dsDNA antibody concentrations were also associated with active renal disease, whereas serum IgA1 anti-dsDNA antibody and IFN-α concentrations were associated with mucocutaneous disease activity but did not predict response to B-cell targeted therapy. Patients with a high baseline serum interleukin-6 concentration were less likely to have a major clinical response, irrespective of therapy.
INTERPRETATION
This exploratory study revealed the presence of distinct molecular networks associated with renal and mucocutaneous involvement, and response to B-cell-targeted therapies, which, if confirmed, could guide precision targeting of advanced therapies for this heterogenous disease.
FUNDING
Versus Arthritis, UCLH Biomedical Research Centre, LUPUS UK, and GSK.
PubMed: 36756239
DOI: 10.1016/S2665-9913(22)00332-0 -
Cilia 2016The freshwater planarian Schmidtea mediterranea has recently emerged as a valuable model system to study basal bodies (BBs) and cilia. Planarians are free-living... (Review)
Review
The freshwater planarian Schmidtea mediterranea has recently emerged as a valuable model system to study basal bodies (BBs) and cilia. Planarians are free-living flatworms that use cilia beating at the surface of their ventral epidermis for gliding along substrates. The ventral epidermis is composed of multiciliated cells (MCCs) that are similar to the MCCs in the respiratory airways, the brain ventricles, and the oviducts in vertebrates. In the planarian epidermis, each cell assembles approximately eighty cilia that beat in a coordinate fashion across the tissue. The BBs that nucleate these cilia all assemble de novo during terminal differentiation of MCCs. The genome of the planarian S. mediterranea has been sequenced and efficient methods for targeting gene expression by RNA interference are available. Defects induced by perturbing the expression of BB proteins can be detected simply by analyzing the locomotion of planarians. BBs are present in large numbers and in predictable orientation, which greatly facilitates analyses by immunofluorescence and electron microscopy. The great ease in targeting gene expression and analyzing associated defects allowed to identify a set of proteins required for BB assembly and function in planarian MCCs. Future technological developments, including methods for transgenic expression in planarians and in related species, will achieve turning free-living flatworms into powerful model systems to study MCCs and the associated human pathologies.
PubMed: 26998257
DOI: 10.1186/s13630-016-0037-1 -
Gait & Posture Oct 2018Walking is an everyday activity that requires modifying patterns based on constraints posed by the environment. Meeting multiple constraints at once increases the...
BACKGROUND
Walking is an everyday activity that requires modifying patterns based on constraints posed by the environment. Meeting multiple constraints at once increases the challenge of modifying motor actions.
RESEARCH QUESTION
We asked if adults' strategies in adapting to spatial and temporal constraints were similar and if they would prioritize one constraint over the other when completing both.
METHODS
Across three tasks, we investigated how adults altered their walking to cope with crossing obstacles (Task 1; N = 30), walking to a metronome beat (Task 2; N = 32), and crossing obstacles while walking to a metronome beat (Task 3; N = 30).
RESULTS
Adults recalibrated to their baseline gait, but showed carryover effects after meeting a temporal constraint (allps>.05). We found an effect on the magnitude of deviation from metronome paces (F(262) = 58.86, p<.01). At the slow pace, participants stepped sooner than the beat, and at the fast pace they stepped later than the beat (all ps<.01). Adults altered the kinematics of their walking in response to a spatial constraint, but changed both the kinematics and kinetics of their walking patterns to meet temporal and combined spatial and temporal constraints. When attempting to meet both a spatial and temporal constraint simultaneously, they stepped sooner than the beat at all metronome paces (all ps<.01).
SIGNIFICANCE
Our findings show separate walking strategies in adapting to spatial and temporal constraints. The presence of more than one constraint leads to prioritizing one over the other (i.e., a spatial constraint over a temporal constraint). These findings highlight that strategies for meeting constraints are dependent upon the type and number of constraints presented.
Topics: Adaptation, Physiological; Adult; Biomechanical Phenomena; Gait; Gait Analysis; Humans; Kinetics; Spatial Processing; Task Performance and Analysis; Walking
PubMed: 30125715
DOI: 10.1016/j.gaitpost.2018.08.009 -
PloS One 2015Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that...
Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that certain rhythmic processes in music and language rely on overlapping resources. However, a lack of understanding about how rhythm skills relate to each other has impeded progress in understanding how language relies on rhythm processing. In particular, it is unknown whether all rhythm skills are linked together, forming a single broad rhythmic competence, or whether there are multiple dissociable rhythm skills. We hypothesized that beat tapping and rhythm memory/sequencing form two separate clusters of rhythm skills. This hypothesis was tested with a battery of two beat tapping and two rhythm memory tests. Here we show that tapping to a metronome and the ability to adjust to a changing tempo while tapping to a metronome are related skills. The ability to remember rhythms and to drum along to repeating rhythmic sequences are also related. However, we found no relationship between beat tapping skills and rhythm memory skills. Thus, beat tapping and rhythm memory are dissociable rhythmic aptitudes. This discovery may inform future research disambiguating how distinct rhythm competencies track with specific language functions.
Topics: Adolescent; Female; Humans; Language; Male; Memory; Music
PubMed: 26376489
DOI: 10.1371/journal.pone.0136645