Sustained Increase Research Articles

Differential Cardiac Responses after Passive Leg Raising.

This study retrospectively examined the hemodynamic effects of passive leg raising (PLR) in mechanically ventilated patients during fluid removal before spontaneous breathing trials. In previous studies, we noticed varying cardiac responses after PLR completion, particularly in positive tests. Using a bioreactance monitor, we recorded and analyzed hemodynamic parameters, including stroke volume and cardiac index (CI), before and after PLR in post-acute ICU patients. We included 27 patients who underwent 60 PLR procedures. In preload-unresponsive patients, no significant CI changes were observed (CI_t-6 = 3.7 [2.6; 4.7] mL/min/m2 vs. CI_t9 = 3.3 [2.5; 3.4] mL/min/m2; p = 0.306), while in preload-responsive patients, two distinct CI response types to PLR were identified: a transient peak with immediate return to baseline (CI_t-6 = 2.7 [2.5; 3.1] mL/min/m2 vs. 3.3 [2.6; 3.8] L/min/m2; p = 0.119) and a sustained CI elevation lasting beyond the PLR maneuver (CI_t-6 = 2.8 [2.3; 2.9] L/min/m2 vs. 3.3 [2.8; 3.9] ml/min/m2; p = 0.034). The latter was particularly noted when ΔCI during PLR exceeded 25%. Our findings suggest that in certain preload-responsive patients, PLR can induce a more sustained increase in CI, indicating a possible persistent hemodynamic effect. This effect could be due to a combination of autotransfusion and sympathetic activation affecting venous return and vascular tone. Further research in larger cohorts and more comprehensive hemodynamic assessments are warranted to validate these observations and elucidate the possible underlying mechanisms.The Fluid unLoading On Weaning (FLOW) study was prospectively registered under the ID NCT04496583 on 2020-07-29 at ClinicalTrials.gov.

Case Studies on Pre-eruptive X-class Flares using R-value in the Lower Solar Atmosphere

The R-value is a measure of the strength of photospheric magnetic polarity inversion lines in active regions (ARs). This work investigates the possibility of a relation between R-value variations and the occurrence of X-class flares in ARs, not in the solar photosphere, as usual, but above it in regions closer to where flares occur. The modus operandi is to extrapolate the Solar Dynamic Observatory’s Helioseismic and Magnetic Imager magnetogram data up to a height of 3.24 Mm above the photosphere and then compute the R-value based on the extrapolated magnetic field. Recent studies have shown that certain flare-predictive parameters such as the horizontal gradient of the vertical magnetic field and magnetic helicity may improve flare prediction lead times significantly if studied at a specific height range above the photosphere, called the optimal height range (OHR). Here, we define the OHR as a collection of heights where a sudden but sustained increase in R-value is found. For the eight case studies discussed in this paper, our results indicate that it is possible for OHRs to exist in the low solar atmosphere (between 0.36 and 3.24 Mm), where R-value spikes occur 48–68 hr before the first X-class flare of an emerging AR. The temporal evolution of R-value before the first X-class flare for an emerging AR is also found to be distinct from that of nonflaring ARs. For X-class flares associated with nonemerging ARs, an OHR could not be found.

The role of autonomic imbalance in the pathogenesis of hypertension and the therapeutic effectiveness of renal denervation (literature review)

Arterial hypertension (AH) remains a global problem of modern healthcare, since, despite advances in clinical pharmacology and the use of modern antihypertensive drugs, it continues to be a major risk factor for cardiovascular complications. This necessitates a more in-depth study of the pathogenetic mechanisms of this disease and the development of new pathogenetically based methods of its treatment. Every year more and more studies are published, the results of which indicate the significant role of autonomic imbalance in the pathogenesis of the disease. The article presents the main modern data concerning the study of this problem. A detailed analysis of works devoted to the role of sympathetic hyperactivation in a sustained increase in blood pressure (BP) and the development of pharmacotherapy-resistant forms of hypertension (RAH) was carried out. Particular attention is paid to the influence of modern endovascular methods on changes in the severity of immunoinflammatory processes, through the activation of which the hypertensive effects of increased activity of the sympathetic nervous system are realized. Possible mechanisms of the therapeutic effectiveness of renal denervation and prospects for further clinical application of the method are described.

First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments

BackgroundTumor-selective oncolytic viral vectors are promising anticancer therapeutics; however, challenges with dosing and potency in advanced/metastatic cancers have limited efficacy and usage. NG-350A is a next-generation blood-stable adenoviral vector engineered...

RLIM-specific activity reporters define variant pathogenicity in Tonne-Kalscheuer syndrome

Tonne-Kalscheuer syndrome (TOKAS, OMIM # 300978) is an X-linked recessive disorder with devastating consequences for patients such as intellectual disability, developmental delay, and multiple congenital abnormalities. TOKAS is associated with hemizygous variants in the RLIM gene that encodes a RING-type E3 ubiquitin ligase. The current sustained increase in reported RLIM variants of uncertain significance creates an urgent need to develop assays that can screen these variants and experimentally determine their pathogenicity and disease association. Here, we engineered flow cytometry-based RLIM-specific reporters to measure RLIM activity in TOKAS. This paper describes the design and use of RLIM-specific reporters to determine the pathogenicity of a TOKAS RLIM gene variant. Our data demonstrates that RLIM-specific flow cytometry reporters based on either the full length or a degron region of the substrate REX1 measure RLIM activity in cells. Further, we describe the TOKAS variant RLIM p.Asn581Lys and using reporter assays, determine that it disrupts RLIM catalytic activity. This data reveals how the p.Asn581Lys variant impairs RLIM function and suggests pathogenic mechanisms. The use of RLIM-specific reporters will greatly accelerate the resolution of variants of uncertain significance and disease association in TOKAS.

Rising out-of-hospital mortality in Canada during 2020‒2022: A striking impact observed among young adults.

Out-of-hospital mortality rates surged during the early COVID-19 pandemic. While expecting a return to pre-pandemic levels, the evolving patterns of out-of-hospital mortality in Canada remain uncertain. We investigated whether these rates returned to pre-pandemic levels. This retrospective study, employing linked administrative data, analyzed out-of-hospital mortality trends among adult residents in Ontario, Alberta, and Nova Scotia. Interrupted time series analysis assessed trends in age- and sex-standardized rates/100,000/quarter during pre-pandemic (April 2014-March 2020) and pandemic periods (April 2020-March 2022), while considering April to June 2020 as the pandemic onset period. Crude mortality rates were also examined, stratified by sex and age groups. Pre-pandemic, Ontario's standardized out-of-hospital mortality rates were rising, while Alberta's and Nova Scotia's remained stable. At the pandemic onset, all provinces experienced significant increases in standardized out-of-hospital mortality rates/100,000 (Ontario: β 14.6, 95% CI [3.97, 25.22]; Alberta: 21.3, 95% CI [9.26, 33.34]; Nova Scotia: 10.5, 95% CI [1.06, 19.88]). During the pandemic, standardized out-of-hospital mortality rates/100,000/quarter remained above pre-pandemic levels, with no significant departure from the increased pandemic onset levels (Ontario: - 1.6, 95% CI [- 3.63, 0.52]; Alberta: 0.45, 95% CI [- 1.47, 2.36]; Nova Scotia: - 0.06, 95% CI [- 2.18, 2.06]). Crude out-of-hospital mortality rates increased most prominently among individuals aged 18 to 45 in Alberta and Ontario, and among males across all provinces. The sustained increase in out-of-hospital mortality, observed from the pandemic's onset, spanning more than 2years, potentially suggests its persistent direct and indirect effects on population health in Canada.

Inhibition of calpain reduces oxidative stress and attenuates pyroptosis and ferroptosis in Clostridium perfringens Beta-1 toxin-induced macrophages

Clostridium perfringens Beta-1 toxin (CPB1) is a lethal toxin, which can lead to necrotic enteritis, but the pathological mechanism has not been elucidated. We investigated whether reactive oxygen species (ROS) participated in CPB1-induced pyroptosis and ferroptosis, and investigated the effects of calpain on CPB1-induced oxidative stress and inflammation. Scavenging ROS by N-acetyl cysteine (NAC) led to the reduction of ROS, inhibited the death of macrophages, cytoplasmic swelling and membrane rupture, the expression of pyroptosis-related proteins and proinflammatory factor, while increased the expression of anti-inflammatory factors in cells treated with rCPB1. Adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1 (ATP5A1) was identified specifically interact with rCPB1. Silencing ATP5A1 inhibited accumulation of ATP and ROS, leaded to less cytoplasmic swelling and membrane rupture, attenuated pyroptosis and inflammation in rCPB1-treated cells. We also found that rCPB1 induces ferroptosis in macrophages, and the level of ferroptosis was similar with H2O2. Of note, H2O2 is a major ROS source, indicated that ROS production may play a major role in the regulation of ferroptosis in macrophages treated with rCPB1. This finding was further corroborated in rCPB1- induced human acute monocytic leukemia cells, which were treated with NAC. In addition, the inhibition of ferroptosis using liproxstatin-1 inhibited the shriveled mitochondrial morphology, increased the expression of glutathione peroxidase 4, nicotinamide adenine dinucleotide (phosphate) hydrogen: quinone oxidoreductase 1 and cysteine/glutamic acid reverse transport solute carrier family 7 members 11, decreased the expression of heme oxygenase 1, nuclear receptor coactivator 4 and transferrin receptor proteins, reduced malondialdehyde and lipid peroxidation levels, and increased intracellular L-glutathione levels in cells treated with rCPB1. Furthermore, calpain inhibitor PD151746 was used to investigate how pyroptosis and ferroptosis were involved simultaneously in rCPB1-treated macrophages. We showed that PD151746 inhibited ATP and ROS production, reversed the representative pyroptosis/ferroptosis indicators and subsequently reduced inflammation. The above findings indicate that rCPB1 might lead to macrophage pyroptosis and ferroptosis through the large and sustained increase in intracellular calpain and oxidative stress, further lead to inflammation.

Trends in medicine utilisation in public and private healthcare facilities before and during COVID-19: a nationwide analysis of medicine procurement and sales data, 2018-2022.

There was a fluctuation in medication demand and supply during COVID-19 pandemic. This study aimed to assess the trend of drug utilisation in Malaysia in 2018-2022 and evaluate the impact of COVID-19 on drug utilisation rates. We conducted a repeated cross-sectional study of pharmaceutical sales data from public and private sectors in Malaysia from 2018 to 2022. Drug utilisation rates for the period after the onset of COVID-19 (2020-2022) was compared with the earlier period (2018-2019). Interrupted time-series regression analyses evaluated level and slope changes compared to pre-COVID-19 pandemic level for quarterly rates of drugs utilisation in public and private sectors. There was an immediate reduction in the utilisation rates for all drugs after COVID-19 in public (-20.4%; p = 0.043) and private sectors (-22.4%; p = 0.003). In both sectors, significant level changes were observed for anti-infectives, musculoskeletal, neurological, respiratory, and sensory organs preparations following COVID-19 pandemic, followed by a sustained increase in trend from 2020 to 2022. Public sector had a 22.2% reduction in the utilisation of cardiovascular drugs (p = 0.002), particularly for renin-angiotensin system (RAS) agents (-47.4%, p = 0.019). Private sector had large changes for anti-infectives (-53.6%, p < 0.001) and neurological drugs (-51.4%, p < 0.001), driven by an immediate level reduction in antibacterials (-54.2%, p < 0.001) and cough and cold preparations (-59.2%, p < 0.001). Classes with agents used for COVID-19 treatment, such as systemic corticosteroids, antibiotics, and antivirals had an increasing trend between April 2020 and December 2022, although some slope changes were not statistically significant. A significant reduction in the overall drug utilisation rates was observed in the public and private sectors in Malaysia as an immediate impact of the COVID-19 pandemic in 2020. The impacts varied by therapeutic class and health sector. This finding provides an understanding of the changing patterns of drug utilisation that were affected by disease outbreaks for future planning of pandemic preparedness.

Impact of codeine rescheduling on prescribing of codeine and other opioids: Interrupted time series analyses using Australian general practice data.

We aimed to determine the impact of codeine rescheduling on prescribing of codeine and other opioids, with a focus on demographic and diagnoses associated with codeine prescribing before and after rescheduling of codeine to prescription-only in February 2018. We used interrupted time series analysis (February 2016-February 2020) and probit regression to examine prescribing of codeine and other opioids according to primary care data from 464 general practice clinics in Victoria, Australia. The rate of codeine prescribing increased in the month following rescheduling (additional 76 people/10000, 95% confidence interval [CI] 49-103), then declined to baseline rates (slope -2.02, 95% CI 3.79, -0.25). Prescribing of other opioids did not change. Post rescheduling, females were more likely to receive codeine prescriptions compared to males (β=0.094, 95% CI 0.08-0.108) and those aged 70-79 years were more likely to receive codeine compared to those aged <30 years. Those residing in the least disadvantaged areas had a greater probability of being prescribed codeine than those in more disadvantaged areas after rescheduling (β =0.154, 95% CI 0.129-0.179). A documented mental health diagnosis (β =0.067, 95% CI 0.052-0.082) or migraine diagnosis (β =0.057, 95% CI 0.037-0.078) was associated with increased likelihood of receiving a codeine prescription after rescheduling compared to before in contrast to those without such a diagnosis. Codeine rescheduling did not result in a sustained increase in codeine prescribing nor a change in the prescribing of other opioids. Patient factors associated with increased codeine prescribing after compared to before rescheduling included female sex, older age, migraine diagnosis and comorbid mental health conditions. EU PAS Register (EUPAS43218).

Comparison between standard hematological parameters and blood doping biomarkers in dried blood spots within the athlete population of Swiss Sport Integrity.

The study demonstrated the feasibility of incorporating RNA biomarkers, specifically 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), to improve the hematological module of the Athlete Biological Passport (ABP) in routine antidoping context. The aim was to investigate the implementation of reticulocyte (RET) related biomarkers, specifically ALAS2 and CA1, using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on dried blood spots (DBS) from elite athletes. Hemoglobin changes over time in DBS samples was measured as well. Combining hemoglobin and messenger RNA (mRNA) analyses allowed to monitor alterations of the established marker, "DBS OFF-score". Ten athletes were selected for sampling by the Swiss national antidoping organization, Swiss Sports Integrity (SSI). Samples were collected, transported and analyzed for ABP following the World Anti-Doping Agency (WADA) procedures and spotted onto Protein Saver DBS cards. Most athletes exhibited stable biomarker levels, except for one individual involved in ski mountaineering, who demonstrated a sustained increase in ALAS2 compared to the individual baseline. This elevation could be due to blood withdrawal or other factors, such as doping with substances outside the targeted test menu. In this study, RNA-biomarkers were successfully analyzed in routine blood samples, and the project demonstrated promising results for the implementation of ALAS2 and CA1 in routine analysis to complement the ABP.

Landscape pattern prediction method based on ANN-CA-Markov coupling model

The simulation and prediction of landscape patterns can provide a reference for the formulation of ecological space security policies and management and control measures. Therefore, it is necessary to use objective and accurate scientific methods to make accurate simulation predictions. In this study, the quantitative prediction of the Markov model is combined with the advantages of the space-time simulation of the CA model, and the artificial neural network (ANN) module is used for calculation and coupling correction. The Kappa coefficient and the FoM (figure of merit) index are used to test the simulation accuracy. Based on this process, the changes of the landscape pattern in Mudanjiang City at three time points in 2000, 2010 and 2020 were analyzed, and the simulation prediction was made based on this. The experimental results show that the CA-Markov model using the ANN module for coupling correction can be tested for accuracy in the study area, and its Kappa coefficient is 0.834 and the FoM index is 0.001. The model meets the requirements of the landscape pattern for the accuracy of simulation and prediction, and the prediction and analysis of the study area is carried out, and the accurate prediction results are obtained.The results of the study were: Looking at the change in landscape pattern over the 20 years from 2000 to 2020, significant changes occurred in the areas of arable land and artificial surface. The total area of arable land decreased by nearly 130 km2, while the area of artificial surface (i.e., built-up land) increased by about 167 km2. The forest area initially decreased and then increased, with an overall increase of approximately 56 km2, while the water and grassland areas first increased and then decreased. In terms of spatial distribution, the changes in agricultural and forest land are mainly concentrated in the central area where urban development is intensive and in the northern forest area. The results of this study are quite important for policy formulation, according to which it was found that human activities, especially urbanization, have led to a decrease in the area of forested land, and therefore the implementation of the natural forest protection policy can lead to a sustained increase in the area of forested land.

Research progress on isotope tracing on the sources and transformations of reactive nitrogen in the earth-atmosphere system.

Since the Industrial Revolution, human activities have led to a rapid and sustained increase in reactive nitrogen production, resulting in nitrogen enrichment at the Earth's surface and triggering many ecological and environmental issues. Stable isotopes are effective tools for tracing the sources and mechanisms of environmental processes. The nitrogen isotope values in surface environments integrate the isotope signatures of different nitrogen sources and the isotope fractionation effects of transformation processes. The composition of nitrogen isotopes can thus be utilized to trace the sources and cycling of nitrogen at the surface, aiding the development of strategies to reduce reactive nitrogen emissions, and assess the ecological effects of nitrogen enrichment. We reviewed the research progress on nitrogen isotope in the sources of reactive nitrogen in atmospheric systems, plant nitrogen utilization, and tracking of nitrogen processes in forest ecosystems. We further discussed how to gain a more systematic and accurate understanding of nitrogen cycle within and between the various spheres of the surface environment.

362 Nutrikinetic evaluation and modeling of 25-hydroxyvitamin D3 in beef cattle

Abstract The objective of this study was to evaluate serum 25-hydroxyvitamin D3 [25(OH)D3] status in beef cattle when 1) fed diets with supplemental 25(OH)D3 or calcidiol (HyD, dsm-firmenich, Plainsboro, NJ), and 2.) a single dose of calcidiol was administered to cannulated heifers on nutrikinetic evaluation and predictive modeling simulations. In experiment 1, crossbred heifer calves [n = 96, initial body weight (BW) = 222 ± 12.4 kg] were assembled from auction markets near Dickson, TN and transported ~1,069 km to Manhattan, KS. Heifers (n = 12 per pen) were stratified by BW and randomly allocated to a corn-based receiving diet with one of four dietary treatments: 1) No supplemental D3 or calcidiol (CON, n = 24), 2) 3,000 IU supplemental D3·heifer⁻¹·d⁻¹ (D3, n = 24), 3.) 0.5 mg calcidiol/h/d (Hy D Low, n = 24), or 4.) 1.0 mg calcidiol·heifer⁻¹·d⁻¹ (Hy D High, n = 24) for 60 d. Blood samples were collected from each heifer prior to transport (d -1), on arrival (d 0) and on d 14, 31, and 60 of dietary treatment period. Data were analyzed using the GLIMMIX procedure of SAS using animal as experimental unit and treatment as fixed effect. HyD High calves had greater (P &amp;lt; 0.001) serum 25(OH)D3 concentrations than HyD Low at d 14 and 31 (Figure 1 and 2). At d 14, 31 and 60, HyD High and HyD Low calves had greater (P &amp;lt; 0.001) serum 25(OH)D3 concentrations than CON or D3 treatments. In experiment 2, cannulated crossbred heifers (n = 8, initial BW = 289 ± 44.9 kg were randomly assigned to one of two treatments: 1.) 3 mg/272 kg BW calcidiol, or 2.) 5 mg/272 kg BW calcidiol in a single dose administered via rumen cannula at h 0. Serial blood samples were collected at baseline out to 70 d post-dose. Serum 25(OH)D3 concentrations were analyzed via HPLC coupled with tandem MS (dsm-firmenich, Belvidere, NJ). Predictive modeling simulations of serum 25(OH)D3 concentrations used non-parametric superposition (Certara Phoenix WinNonlin 64, St. Louis, MO) from applying non-compartmental analysis with the assumptions of linearity, independent calcidiol dose response, and the rate of absorption and the average systemic clearance were consistent for each calcidiol dosing interval. The elimination half-life (t1/2) of calcidiol was determined to be an average of 7.1 d and area under change in concentration-time curve time 0 to the last time point that measured above baseline concentration post dose (AUC0-last) averaged of 32.6 d (Table 1). Non-parametric dosing simulations using nutrikinetic parameters from experiment 2 suggest that administration of two 5 mg oral doses of calcidiol with daily feeding of 1 mg would result in a rapid and sustained increase in serum 25(OH)D3. However, simulations should be confirmed in vivo before implementation.

Tracking Varroa Parasitism Using Handheld Infrared Cameras: Is Eusocial Fever the Key?

The Varroa destructor is the most significant bee parasite and the greatest threat to bee health all around the world. Due to its hidden lifestyle, detection within the brood cell is only possible through invasive techniques. Enhancing detection methods is essential for advancing research on population dynamics, spread, selection efforts, and control methodologies against the mite. In our study, we employed infrared imaging to measure the thermal differences in parasite and intact Apis mellifera worker broods. Experiments were conducted over two years at the MATE Kaposvár Campus in Hungary involving five beehives in 2022 and five beehives in 2023. A FLIR E5-XT WIFI handheld infrared camera was used to create a heat map of capped brood frames. Our results indicate that the resolution of these cameras is sufficient to provide detailed IR images of a bee colony, making them suitable to detect temperature differences in intact and Varroa parasitized capped brood cells. Mite parasitism causes a time-dependent and sustained temperature increase in developing bee pupae, observable regardless of mite number. Our work demonstrates two different heating patterns: hotspot heating and heating cells that are responsible for the elevated temperature of the Varroa-infested cells as a social fever response by the worker bees. Based on our results, future research combined with AI-based image evaluation software could offer beekeepers and researchers practical and valuable tools for high-throughput, non-invasive Varroa detection in the field.

101 5-HT4 receptor-mediated vasorelaxation occurs through a cyclic mononucleotide-dependent mechanism in the isolated bovine lateral saphenous vein

Abstract Serotonin (5-HT)-mediated vasorelaxation of the isolated bovine lateral saphenous vein occurs primarily through 5-HT4 receptor activation. Vasorelaxation responses mediated through 5-HT4 have only been documented to occur in cattle and sheep and thus, may represent a novel vasorelaxation mechanism that is specific to ruminants. In tissues from other species, the 5-HT4 receptor and its associated G protein couple with adenylate cyclase. However, the mechanisms contributing to 5-HT4-mediated vasorelaxation in vascular tissue remain undefined. To better understand the mechanisms of 5-HT4-mediated vasorelaxation, lateral saphenous veins from cattle (n = 4) were collected and assessed for vasoactivity in response to increasing concentrations of a selective 5-HT4 receptor agonist (BIMU-8) in the absence and presence of selective inhibitors of downstream proteins involved with cyclic mononucleotide-mediated signaling. Isolated vessel segments were suspended in chambers of a multi-myograph containing 5 mL of continuously oxygenated Krebs-Henseleit buffer and equilibrated to 1 g tension for 90 min. After the equilibration period, vessels were exposed to dimethyl sulfoxide (DMSO; vehicle control) or selective inhibitors of downstream protein targets dissolved in DMSO (1×10-5 M) for 5 min. Vessels were pre-contracted with 1×10-4 M phenylephrine for 10 min to achieve a sustained increase in tension. After the 10-min pre-contraction period, vessels were exposed to increasing concentrations (1×10-9 to 1×10-4) of BIMU-8 non-cumulatively. Vasoactive response data were normalized as a percentage of the maximum contractile response induced by the phenylephrine pre-contraction. In the absence of selective inhibitors (control), BIMU-8 induced (P &amp;lt; 0.01) dose-dependent relaxations (mean -log EC50 = 6.30 M) with a 112% increase in maximal vasorelaxation activity occurring at 1×10-4 M. In the presence of the selective inhibitors for adenylate cyclase (NKY80) or guanylate cyclase (NS2028), 66% and 86% of the vasorelaxation responses to BIMU-8 were attenuated (P &amp;lt; 0.01), respectively. In the presence of the selective inhibitors for protein kinase A [protein kinase A inhibitor fragment (6-22) amide] or protein kinase G (Rp-8-bromo-PET-Cyclic GMPS), 66% and 97% of the maximal vasorelaxation responses to BIMU-8 were attenuated (P &amp;lt; 0.01), respectively. In the presence of non-selective inhibitors for Ca2+ channels and K+ channels, vasorelaxation responses to BIMU-8 were attenuated (P &amp;lt; 0.01). In the presence of selective inhibitors for the protein phosphatase 1 and 2A subunits of myosin light chain (calyculin A) and heat shock protein synthesis (quercetin), vasorelaxation responses to BIMU-8 were attenuated (P &amp;lt; 0.01). The findings of the current study demonstrate that 5-HT4-receptor mediated vasorelaxation occurs through a cyclic mononucleotide-dependent mechanism involving cross-activation of protein kinase A and G signaling. Downstream proteins involved in the signaling cascade leading to vasorelaxation include Ca2+ channels, K+ channels, myosin light chain phosphatase, and heat shock proteins. More research is needed to fully describe the cellular and molecular mechanisms responsible for 5-HT4 receptor-mediated vasorelaxation.

Acute and prolonged effects of Bacillus amyloliquefaciens GF424-derived SOD on antioxidant defense in healthy individuals challenged with intense aerobic exercise

Reactive oxygen species (ROS) play a vital role in cellular functions but can lead to oxidative stress and contribute to degenerative diseases when produced in excess. Maintaining redox balance is essential and can be achieved through innate defense mechanisms or external antioxidants. Superoxide dismutase (SOD) is a key enzyme that mitigates intracellular oxidative stress by converting harmful free radicals into hydrogen peroxide, which is subsequently neutralized by catalase and glutathione peroxidase. Previous studies have demonstrated the antioxidant capabilities of SOD derived from Bacillus amyloquefaciens GF424 (BA-SOD) in murine models exposed to either irradiation or SOD1 gene deletion. In this study, a randomized clinical trial was conducted to evaluate the antioxidative benefits of BA-SOD in healthy individuals undergoing acute aerobic exercise (AAE). Eighty participants were randomly assigned to receive either BA-SOD or a placebo for 8 weeks. Antioxidant enzyme activities and glutathione levels were measured before, immediately after, and 30 min post-exercise. A single dose of BA-SOD significantly reduced ROS levels induced by AAE, primarily by enhancing SOD activity in erythrocytes and activating glutathione peroxidase. Continuous BA-SOD administration was associated with a sustained increase in catalase activity and elevated levels of reduced glutathione (GSH). Transcriptomic and metabolomic analyses revealed that a single BA-SOD dose facilitated GSH oxidation, as evidenced by decreased levels of serine, glutamine, and glycine, and increased pyroglutamate levels. Additionally, repeated dosing led to increased expression of genes encoding isocitrate dehydrogenase and malic enzyme, which are involved in NADPH synthesis, as well as nicotinamide phosphoribosyl transferase and NAD kinase, which are essential for NADP availability–critical for converting oxidized glutathione (GSSG) back to GSH. These molecular insights align with clinical observations, suggesting that both acute and long-term BA-SOD supplementation may effectively enhance antioxidant defenses and maintain redox balance under oxidative stress conditions.

Zoom Boom or Bust? Understanding Post-Pandemic Interest in Facial Plastic Surgery via Google Trends.

To understand post-pandemic interest in plastic surgery procedures via Joinpoint analysis of Google Trends search data. Google Trends was used to quantify search volumes from January 2019-December 2022 for select cosmetic face and body procedures in the United States. A keyword analytic tool (Keywords Everywhere) extracted absolute search volumes (average monthly searches). Joinpoint analysis assessed search trends over time reported as monthly percentage change (MPC). All procedures queried, including a non-cosmetic control (cataract surgery), demonstrated expected declines at the start of the COVID-19 pandemic. Blepharoplasty, face lift, neck lift, and Botox demonstrated statistically significant increase in search volumes that remained elevated relative to pre-pandemic levels. Rhinoplasty, fillers, and abdominoplasty interest increased initially followed by return to pre-pandemic levels by the end of 2022. The remainder of search terms did not show a clear temporal associated with COVID-19 lockdowns. The "Zoom Boom" appears to be a real phenomenon reflected by sustained increase in public interest in relation to facial plastic procedures. NA Laryngoscope, 2024.

Unravelling the interplay between Harmattan wind and baroreflex functions: implications on environmental health and cardiovascular pathophysiology

Harmattan is a season characterized by dust, cold, and sub-humid trade winds in Sub-Saharan countries. It’s similar to meteorological phenomena like Asian dust storms, Santa Ana winds, Australian bushfires, and Saharan dust in the Caribbean. It causes profound changes in the cardiorespiratory system in apparently healthy individuals and increases the risk of hospitalization in susceptible individuals. Exposure to these extreme conditions has been associated with alterations in autonomic function and baroreceptor sensitivity thus resulting in dysregulation of blood pressure control mechanisms. Baroreceptors are critical regulators of hemodynamics and cardiovascular function. They play a vital role in the short-term responses to blood pressure perturbation and are essential for acute restoration of blood pressure following cold exposure. Harmattan wind contains a barrage of chemicals, dust, and particulate matters depending on industrialization, natural and human activities. Particulate matter from Harmattan dust can trigger systemic inflammation and oxidative stress, exacerbating endothelial dysfunction and impairing vascular reactivity thus contributing to the pathogenesis of alterations in baroreceptor insensitivity, and cardiovascular diseases, including hypertension and atherosclerosis. Furthermore, fine particulate matter from dust may penetrate deep into the respiratory tract, activating pulmonary sensory receptors and eliciting reflex responses that influence autonomic tone. The presence of rich acrolein smokes and non-essential heavy metals such as cadmium, lead, and mercury in Harmattan wind also reduces baroreflex sensitivity, culminating in a sustained increase in diastolic and systolic blood pressure. This integrated review aims to provide valuable insights into how changes in each of these environmental constituents alter vital pathophysiologic and immunologic mechanisms of the body leading to baroreceptor instability and ultimately hemodynamic imbalance using available primary studies. Understanding this intricate interplay is crucial for implementing targeted interventions and informed public health strategies to mitigate the adverse effects of extreme environmental exposure and ultimately reduce poor health outcomes in the affected regions.

Child Mental Health, Homelessness, and the Shelter System: Evidence from Medicaid in New York City.

We identified children who resided in the New York City shelter system during 2015-2020 by matching address histories in Medicaid insurance claims to publicly available homeless shelter addresses, permitting examination of health care use before, during, and after shelter stays. We found that 4.5% of NYC children aged 4-17 with consistent Medicaid coverage entered shelter over a three-to-five-year period. After shelter entry, children had increased probabilities of receiving mental health services, including therapy and diagnoses of neurodevelopmental disorders, but little change in physical health service use. Children placed in shelters co-located with mental health services were similar to children entering other shelters prior to entry but had particularly large and sustained increases in use of mental health services afterwards. Children without prior mental health claims placed in shelters co-located with mental health services were 38-48% more likely to receive mental health therapy and 14-16% more likely to receive neurodevelopmental diagnoses than similar children placed elsewhere. These children were also more likely to receive Supplemental Security Income and stayed in shelter longer. This example illustrates the potential of linking administrative data sets in order to study vulnerable populations.

Middle Ordovician paleoenvironmental evolution of the western Laurentian carbonate platform: Evidence for persistent oxygenation of the shallow ocean and implications for biodiversification

The Great Ordovician Biodiversification Event (GOBE) encompasses a series of rapid and sustained diversification pulses unparalleled in Earth history. Despite the uniqueness and magnitude of the GOBE, a singular driving force for this critical interval has not been identified. Multiple hypotheses have been presented, some pairing the GOBE as cause and effect with extrinsic factors such as changing global temperatures, ocean chemistry, or paleogeography, while others have pointed to factors intrinsic to biology itself, such as the proliferation of skeletonization, predator-prey escalation, or the development of complex tiered seafloor communities. Sufficient data are not available at present to ascertain what combination of these factors was the key to generating the GOBE.Here, we present new paired carbon and sulfur isotope data (δ13Ccarb, δ13Corg, and δ34SCAS), along with iodine concentration data from a Darriwilian carbonate sequence exposed at Meiklejohn Peak in southwestern Nevada, USA. Within a detailed lithologic and biostratigraphic framework, these new data provide a robust correlation to chemostratigraphic zonation established in Baltica and eastern Laurentia along with insights into the evolution of Middle Ordovician biogeochemical cycling. Carbon isotope data indicate a slight (2 ‰) increase in the fractionation between carbonate carbon and organic matter (Δ13C) during the onset of the middle Darriwilian carbon isotope excursion (MDICE), and new carbonate-associated sulfate (CAS) sulfur isotope data are consistent with a decrease in global pyrite burial during this time. Both of these observations support previous work arguing for a synchronous increase in the [O2] of the global oceans. New iodine concentration data from Meiklejohn Peak also suggest a progressive and sustained increase in the [O2] of regional waters throughout the Darriwilian during a period of relative sea-level highstand. This expansion of stable and well‑oxygenated ecospace could have laid the foundation for rapid diversification during one of the largest pulses of the GOBE.