Personal Exposure to Submicrometer Particles and Heart Rate Variability in Human Subjects

We conducted a study on two panels of human subjects—9 young adults and 10 elderly patients with lung function impairments—to evaluate whether submicrometer particulate air pollution was associated with heart rate variability (HRV). We measured these subjects’ electrocardiography and personal exposure to number concentrations of submicrometer particles with a size range of 0.02–1 μm (NC(0.02–1)) continuously during daytime periods. We used linear mixed-effects models to estimate the relationship between NC(0.02–1) and log(10)-transformed HRV, including standard deviation of all normal-to-normal intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), low frequency (LF, 0.04–0.15 Hz), and high frequency (HF, 0.15–0.40 Hz), adjusted for age, sex, body mass index, tobacco exposure, and temperature. For the young panel, a 10,000-particle/cm(3) increase in NC(0.02–1) with 1–4 hr moving average exposure was associated with 0.68–1.35% decreases in SDNN, 1.85–2.58% decreases in r-MSSD, 1.32–1.61% decreases in LF, and 1.57–2.60% decreases in HF. For the elderly panel, a 10,000-particle/cm(3) increase in NC(0.02–1) with 1–3 hr moving average exposure was associated with 1.72–3.00% decreases in SDNN, 2.72–4.65% decreases in r-MSSD, 3.34–5.04% decreases in LF, and 3.61–5.61% decreases in HF. In conclusion, exposure to NC(0.02–1) was associated with decreases in both time-domain and frequency-domain HRV indices in human subjects

Effects of Particle Size Fractions on Reducing Heart Rate Variability in Cardiac and Hypertensive Patients

It is still unknown whether the associations between particulate matter (PM) and heart rate variability (HRV) differ by particle sizes with aerodynamic diameters between 0.3 μm and 1.0 μm (PM(0.3–1.0)), between 1.0 μm and 2.5 μm (PM(1.0–2.5)), and between 2.5 μm and 10 μm (PM(2.5–10)). We measured electrocardiographics and PM exposures in 10 patients with coronary heart disease and 16 patients with either prehypertension or hypertension. The outcome variables were standard deviation of all normal-to-normal (NN) intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), low frequency (LF; 0.04–0.15 Hz), high frequency (HF; 0.15–0.40 Hz), and LF:HF ratio for HRV. The pollution variables were mass concentrations of PM(0.3–1.0), PM(1.0–2.5), and PM(2.5–10). We used linear mixed-effects models to examine the association between PM exposures and log(10)-transformed HRV indices, adjusting for key personal and environmental attributes. We found that PM(0.3–1.0) exposures at 1- to 4-hr moving averages were associated with SDNN and r-MSSD in both cardiac and hypertensive patients. For an interquartile increase in PM(0.3–1.0), there were 1.49–4.88% decreases in SDNN and 2.73–8.25% decreases in r-MSSD. PM(0.3–1.0) exposures were also associated with decreases in LF and HF for hypertensive patients at 1- to 3-hr moving averages except for cardiac patients at moving averages of 2 or 3 hr. By contrast, we found that HRV was not associated with either PM(1.0–2.5) or PM(2.5–10). HRV reduction in susceptible population was associated with PM(0.3–1.0) but was not associated with either PM(1.0–2.5) or PM(2.5–10)

Glycogen synthase kinase 3α and 3β have distinct functions during cardiogenesis of zebrafish embryo

<p>Abstract</p> <p>Background</p> <p>Glycogen synthase kinase 3 (GSK3) encodes a serine/threonine protein kinase, is known to play roles in many biological processes. Two closely related GSK3 isoforms encoded by distinct genes: GSK3α (51 kDa) and GSK3β (47 kDa). In previously studies, most GSK3 inhibitors are not only inhibiting GSK3, but are also affecting many other kinases. In addition, because of highly similarity in amino acid sequence between GSK3α and GSK3β, making it difficult to identify an inhibitor that can be selective against GSK3α or GSK3β. Thus, it is relatively difficult to address the functions of GSK3 isoforms during embryogenesis. At this study, we attempt to specifically inhibit either GSK3α or GSK3β and uncover the isoform-specific roles that GSK3 plays during cardiogenesis.</p> <p>Results</p> <p>We blocked <it>gsk3α </it>and <it>gsk3β </it>translations by injection of morpholino antisense oligonucleotides (MO). Both <it>gsk3α</it>- and <it>gsk3β</it>-MO-injected embryos displayed similar morphological defects, with a thin, string-like shaped heart and pericardial edema at 72 hours post-fertilization. However, when detailed analysis of the <it>gsk3α</it>- and <it>gsk3β</it>-MO-induced heart defects, we found that the reduced number of cardiomyocytes in <it>gsk3α </it>morphants during the heart-ring stage was due to apoptosis. On the contrary, <it>gsk3β </it>morphants did not exhibit significant apoptosis in the cardiomyocytes, and the heart developed normally during the heart-ring stage. Later, however, the heart positioning was severely disrupted in <it>gsk3β </it>morphants. <it>bmp4 </it>expression in <it>gsk3β </it>morphants was up-regulated and disrupted the asymmetry pattern in the heart. The cardiac valve defects in <it>gsk3β </it>morphants were similar to those observed in <it>axin1 </it>and <it>apc</it>^{<it>mcr </it>}mutants, suggesting that GSK3β might play a role in cardiac valve development through the Wnt/β-catenin pathway. Finally, the phenotypes of <it>gsk3α </it>mutant embryos cannot be rescued by <it>gsk3β </it>mRNA, and vice versa, demonstrating that GSK3α and GSK3β are not functionally redundant.</p> <p>Conclusion</p> <p>We conclude that (1) GSK3α, but not GSK3β, is necessary in cardiomyocyte survival; (2) the GSK3β plays important roles in modulating the left-right asymmetry and affecting heart positioning; and (3) GSK3α and GSK3β play distinct roles during zebrafish cardiogenesis.</p

A genetic algorithm-based boolean delay model of intracellular signal transduction in inflammation

Abstract Background Signal transduction is the major mechanism through which cells transmit external stimuli to evoke intracellular biochemical responses. Understanding relationship between external stimuli and corresponding cellular responses, as well as the subsequent effects on downstream genes, is a major challenge in systems biology. Thus, a systematic approach to integrate experimental data and qualitative knowledge to identify the physiological consequences of environmental stimuli is needed. Results In present study, we employed a genetic algorithm-based Boolean model to represent NF-κB signaling pathway. We were able to capture feedback and crosstalk characteristics to enhance our understanding on the acute and chronic inflammatory response. Key network components affecting the response dynamics were identified. Conclusions We designed an effective algorithm to elucidate the process of immune response using comprehensive knowledge about network structure and limited experimental data on dynamic responses. This approach can potentially be implemented for large-scale analysis on cellular processes and organism behaviors. </jats:sec

Computational modeling with forward and reverse engineering links signaling network and genomic regulatory responses: NF-κB signaling-induced gene expression responses in inflammation

<p>Abstract</p> <p>Background</p> <p>Signal transduction is the major mechanism through which cells transmit external stimuli to evoke intracellular biochemical responses. Diverse cellular stimuli create a wide variety of transcription factor activities through signal transduction pathways, resulting in different gene expression patterns. Understanding the relationship between external stimuli and the corresponding cellular responses, as well as the subsequent effects on downstream genes, is a major challenge in systems biology. Thus, a systematic approach is needed to integrate experimental data and theoretical hypotheses to identify the physiological consequences of environmental stimuli.</p> <p>Results</p> <p>We proposed a systematic approach that combines forward and reverse engineering to link the signal transduction cascade with the gene responses. To demonstrate the feasibility of our strategy, we focused on linking the NF-κB signaling pathway with the inflammatory gene regulatory responses because NF-κB has long been recognized to play a crucial role in inflammation. We first utilized forward engineering (Hybrid Functional Petri Nets) to construct the NF-κB signaling pathway and reverse engineering (Network Components Analysis) to build a gene regulatory network (GRN). Then, we demonstrated that the corresponding IKK profiles can be identified in the GRN and are consistent with the experimental validation of the IKK kinase assay. We found that the time-lapse gene expression of several cytokines and chemokines (TNF-α, IL-1, IL-6, CXCL1, CXCL2 and CCL3) is concordant with the NF-κB activity profile, and these genes have stronger influence strength within the GRN. Such regulatory effects have highlighted the crucial roles of NF-κB signaling in the acute inflammatory response and enhance our understanding of the systemic inflammatory response syndrome.</p> <p>Conclusion</p> <p>We successfully identified and distinguished the corresponding signaling profiles among three microarray datasets with different stimuli strengths. In our model, the crucial genes of the NF-κB regulatory network were also identified to reflect the biological consequences of inflammation. With the experimental validation, our strategy is thus an effective solution to decipher cross-talk effects when attempting to integrate new kinetic parameters from other signal transduction pathways. The strategy also provides new insight for systems biology modeling to link any signal transduction pathways with the responses of downstream genes of interest.</p

Critical air pollutant assessments and health effects attributed to PM2.5 during and after COVID-19 lockdowns in Iran: application of AirQ+ models

ObjectivesThe aim of this study was to evaluate changes in air quality index (AQI) values before, during, and after lockdown, as well as to evaluate the number of hospitalizations due to respiratory and cardiovascular diseases attributed to atmospheric PM2.5 pollution in Semnan, Iran in the period from 2019 to 2021 during the COVID-19 pandemic.MethodsDaily air quality records were obtained from the global air quality index project and the US Environmental Protection Administration (EPA). In this research, the AirQ+ model was used to quantify health consequences attributed to particulate matter with an aerodynamic diameter of &lt;2.5 μm (PM2.5).ResultsThe results of this study showed positive correlations between air pollution levels and reductions in pollutant levels during and after the lockdown. PM2.5 was the critical pollutant for most days of the year, as its AQI was the highest among the four investigated pollutants on most days. Mortality rates from chronic obstructive pulmonary disease (COPD) attributed to PM2.5 in 2019–2021 were 25.18% in 2019, 22.55% in 2020, and 22.12% in 2021. Mortality rates and hospital admissions due to cardiovascular and respiratory diseases decreased during the lockdown. The results showed a significant decrease in the percentage of days with unhealthy air quality in short-term lockdowns in Semnan, Iran with moderate air pollution. Natural mortality (due to all-natural causes) and other mortalities related to COPD, ischemic heart disease (IHD), lung cancer (LC), and stroke attributed to PM2.5 in 2019–2021 decreased.ConclusionOur results support the general finding that anthropogenic activities cause significant health threats, which were paradoxically revealed during a global health crisis/challenge

Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a&nbsp;24-hour and 28-day follow-up study

Although zinc oxide nanoparticles (ZnONPs) are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential protein expression, biological processes, molecular functions, and pathways. A total of 18 and 14 proteins displayed significant changes in the lung tissues at 24 hours and 28 days after exposure, respectively, with the most striking changes being observed for S100-A9 protein. Metabolic processes and catalytic activity were the main biological processes and molecular functions, respectively, in the responses at the 24-hour and 28-day follow-up times. The glycolysis/gluconeogenesis pathway was continuously downregulated from 24 hours to 28 days, whereas detoxification pathways were activated at the 28-day time-point after exposure. A comprehensive understanding of the potential time-dependent effects of exposure to ZnONPs was provided, which highlights the metabolic mechanisms that may be important in the responses to ZnONP

Refractory macular hole repaired by autologous retinal graft and blood clot

Background: To evaluate the surgical technique using autologous retinal graft (ARG) and autologous blood clot (ABC) for the management of refractory macular holes (MHs). Methods: This study was a retrospective, consecutive, interventional case series. Six eyes of 6 patients who underwent vitrectomy combined with ARG and ABC for the treatment of refractory MH were reviewed. Visual and anatomic outcomes were evaluated. Results: The mean age was 59.0 ± 9.9 years. All cases had multiple vitreoretinal procedures including vitrectomy and gas fluid exchange before patient presentation. The average numbers of vitrectomies were 2.3 ± 0.5, and those of gas fluid exchange were 3 ± 1.7. Closure of the macular hole was achieved in four (66.7%) cases at last follow-up. The mean follow-up time was 25.2 ± 15.6 months. The averaged BCVA before and after 12 months of the surgery improved from 20/591 to 20/244. Conclusions: This surgical technique using ARG and ABC provide an option for the treatment of refractory MHs

Design and performance of an ultrahigh vacuum spectroscopic-imaging scanning tunneling microscope with a hybrid vibration isolation system

A spectroscopic imaging-scanning tunneling microscope (SI-STM) allows the atomic scale visualization of surface electronic and magnetic structure of novel quantum materials with high energy resolution. To achieve the optimal performance, low vibration facility is required. Here, we describe the design and the performance of an ultrahigh vacuum STM system supported by a hybrid vibration isolation system that consists of a pneumatic passive and a piezoelectric active vibration isolation stages. The STM system is equipped with a 1K pot cryogenic insert and a 9 Tesla superconducting magnet, capable of continuous SI-STM measurements for 7 days. A field ion microscopy system is installed for in situ STM tip treatment. We present the detailed vibrational noise analysis of the hybrid vibration isolation system and demonstrate the performance of our STM system by taking high resolution spectroscopic maps and topographic images on several quantum materials. Our results establish a new strategy to achieve an effective vibration isolation system for high-resolution STM and other scanning probe microscopy to investigate the nanoscale quantum phenomena

Particulate matter is associated with sputum culture conversion in patients with culture-positive tuberculosis

Emerging risk factors for tuberculosis (TB) infection, such as air pollution, play a significant role at both the individual and population levels. However, the association between air pollution and TB remains unclear. The objective of this study was to examine the association between outdoor air pollution and sputum culture conversion in TB patients. In the present study, 389 subjects were recruited from a hospital in Taiwan from 2010 to 2012: 144 controls with non-TB-related pulmonary diseases with negative sputum cultures and 245 culture-positive TB subjects. We observed that a 1 μg/m(3) increase in particulate matter of ≤10 μm in aerodynamic diameter (PM(10)) resulted in 4% higher odds of TB (odds ratio =1.04, 95% confidence interval =1.01–1.08, P<0.05). The chest X-ray grading of TB subjects was correlated to 1 year levels of PM(10) (R(2)=0.94, P<0.05). However, there were no associations of pulmonary cavitation or treatment success rate with PM(10). In subjects with TB-positive cultures, annual exposure to ≥50 μg/m(3) PM(10) was associated with an increase in the time required for sputum culture conversion (hazard ratio =1.28, 95% confidence interval: 1.07–1.84, P<0.05). In conclusion, chronic exposure to ≥50 μg/m(3) PM(10) may prolong the sputum culture conversion of TB patients with sputum-positive cultures