Oxygen Supply Research Articles

Hospital Oxygen Supply Overwhelmed Due to COVID-19: When Demand Exceeds Supply.

During the first wave of COVID-19, we experienced problems with our hospital oxygen supply system. This study aimed to analyze factors that stressed this system and rethink the design criteria of the gas pipeline system considering the varying oxygen demand. A retrospective study was conducted to describe problems that occurred at different stages in the oxygen supply system at our hospital due to increases in oxygen use in general, and the creation of an intermediate respiratory care unit (IRCU) and use of high-flow nasal cannula (HFNC) in particular. Herein, the characteristics and design criteria of the medical gas pipeline system are analyzed, and the steps taken to avoid future problems are outlined. Increases in oxygen use were observed at times of maximum occupancy, and these created vulnerabilities in the oxygen supply due to insufficient capacity in terms of cryogenic tanks, evaporators, and the piping network. The peak consumption was 3 times higher than the peak in the preceding 4 years. The use of HFNC therapy aggravated the problem; IRCU use accounting for as much as two-fifths of the total across the hospital. Steps taken subsequently prevented the recurrence of vulnerabilities. The design criteria for storage and distribution networks of medical gases in hospitals need to be revised considering new parameters for their implementation and the use of HFNC therapy in an IRCU. In particular, the cryogenic tanks, evaporators, and piping network for hospital wards are critical.

A type I and type II chemical biology toolbox to overcome the hypoxic tumour microenvironment for photodynamic therapy.

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality employed for the treatment of various types of cancers, localized infections, and other diseases. Upon illumination, the photo-excited photosensitizer generates singlet oxygen and other reactive species, thereby inducing cytotoxicity in the target cells. The hypoxic tumour microenvironment (TME), however, poses a limitation on the supply of oxygen in tumour tissues. Moreover, under such conditions, tumour metastasis and drug resistance frequently occur, further compromising the efficacy of PDT in combating tumours. Traditionally, type I photosensitizers with lower oxygen consumption demonstrate significant potential in overcoming hypoxic environments and play a crucial role in determining the therapeutic efficacy of PDT because type I photosensitizers can generate highly cytotoxic free radicals. In comparison, type II photosensitizers exhibit high oxygen dependence. The rate of reactive oxygen species (ROS) generation in the type II process is significantly higher than that in the type I process. Thus, the efficiency and selectivity of PDT depend on the properties of the photosensitizer. Here, the recent development and application of type I and type II photosensitizers, mainly in the past year, are summarized. The design methods, electronic structures, photophysical properties, lipophilic properties, electric charge, and other molecular characteristics of these photosensitizers are discussed in detail. These modifications alter the microstructure of photosensitizers and directly impact the results of PDT. The main content of this paper will have a positive promoting and inspiring effect on the future development of PDT.

Simultaneous assessment of blood flow and myelin content in the brain white matter with dynamic [11C]PiB PET: a test-retest study in healthy controls.

Exploring the relationship between oxygen supply and myelin damage would benefit from a simultaneous quantification of myelin and cerebral blood flow (CBF) in the brain's white matter (WM). To validate an analytical method for quantifying both CBF and myelin content in the WM using dynamic [11C]PiB positron emission tomography (PET). A test-retest study was performed on eight healthy subjects who underwent two consecutive dynamic [11C]PiB-PET scans. Three quantitative approaches were compared: simplified reference tissue model 2 (SRTM2), LOGAN graphical model, and standardized uptake value ratio (SUVR). The sensitivity of methods to the size of the region of interest was explored by simulating lesion masks obtained from 36 subjects with multiple sclerosis. Reproducibility was assessed using the relative difference and interclass correlation coefficient. Repeated measures correlations were used to test for cross-correlations between metrics. Among the CBF measures, the relative delivery (R1) of the simplified reference tissue model 2 (SRTM2) displayed the best reproducibility in the white matter, with a strong influence of the size of regions analyzed, the test-retest variability being below 10% for regions above 68 mm3 in the supratentorial white matter. [11C]PiB PET-derived proxies of CBF demonstrated lower perfusion of white matter compared to grey matter with an overall ratio equal to 1.71 ± 0.09 when the SRTM2-R1 was employed. Tissue binding in the white matter was well estimated by the Logan graphical model through estimation of the distribution volume ratio (LOGAN-DVR) and SRTM2 distribution volume ratio (SRTM2-DVR), with test-retest variability being below 10% for regions exceeding 106 mm3 for LOGAN-DVR and 300 mm3 for SRTM2-DVR. SRTM2-DVR provided a better contrast between white matter and grey matter. The interhemispheric variability was also dependent on the size of the region analyzed, being below 10% for regions above 103 mm3 for SRTM2-R1 and above 110 mm3 for LOGAN-DVR. Whereas the 1 to 8-minute standardized uptake value ratio (SUVR1-8) showed an intermediary reproducibility for CBF assessment, SUVR0-2 for perfusion or SUVR50-70 for tissue binding showed poor reproducibility and correlated only mildly with SRTM2-R1 and LOGAN-DVR estimations respectively. [11C]PiB PET imaging can simultaneously quantify perfusion and myelin content in WM diseases associated with focal lesions. For longitudinal studies, SRTM2-R1 and DVR should be preferred over SUVR for the assessment of regional CBF and myelin content, respectively. European Union Clinical Trials Register EUDRACT; EudraCT Number: 2008-004174-40; Date: 2009-03-06; https//www.clinicaltrialsregister.eu ; number 2008-004174-40.

High-flow nasal cannula oxygen reduced hypoxemia in patients undergoing gastroscopy under general anesthesia at ultra-high altitude: a randomized controlled trial.

Hypoxemia can occur in people at ultra-high altitude (above 3500m) even at rest, and patients undergoing gastroscopy under general anesthesia have higher risk of hypoxemia. Supplementary oxygen via standard nasal cannula (SNC) is the standard of care for most patients who undergo gastroscopy under general anesthesia, which provides oxygen flow up to 15L/min. High-flow nasal cannula (HFNC) could deliver oxygen at a rate up to 60L/min, which is recommended by the American Society of Anesthesiologists Practice Guidelines. We speculated that the benefit with HFNC is more prominent in high-altitude areas, and aimed to compare the incidence of hypoxemia during gastroscopy under general anesthesia at ultra-high altitude with oxygen supply via either HFNC or SNC. The trial was registered at at Chinese Clinical Trial Registry (ChiCTR2100045513; date of registration on 18/04/2021). Adult patients undergoing gastroscopy with anesthesia (estimated duration of anesthesia at ≥ 15min) were randomized at a 1:1 ratio to receive HFNC oxygen or SNC oxygen. The primary outcome was hypoxemia (SpO2 < 90% for any duration). Secondary outcomes included severe hypoxemia (SpO2 < 75% for any duration or SpO2 < 90% but ≥ 75% for ≥ 60s) and hypotension, as defined by reduction of mean arterial blood pressure by ≥ 25% from the baseline. A total of 262 patients were enrolled: 129 in the HFNC group and 133 in the SNC group. All patients received the designated intervention. Student's t-test, Mann-Whitney U test and χ2 test were employed in the study. The rate of hypoxemia was 9.3% (12/129) in the HFNC group versus 36.8% (49/133) in the SNC group [risk ratio (95% confidence interval): 0.25(0.14-0.45); P < 0.001). The HFNC group also had lower rate of severe hypoxemia [0.0% (0/129) versus 11.3% (15/133); risk ratio (95% confidence interval): 0.03(0.00-0.55); P < 0.001, respectively]. The rate of hypotension did not differ between the 2 groups [22.5% (29/129) in HFNC group versus 21.1% (28/133) in SNC group; risk ratio (95% confidence interval): 1.07(0.67-1.69) ; P = 0.779]. HFNC oxygen reduced the incidence of hypoxemia during anesthesia in adult patients undergoing gastroscopy at ultra-high altitude.

Modelling medical oxygen supply chain network under demand uncertainty using stochastic programming

Modelling medical oxygen supply chain network under demand uncertainty using stochastic programming

Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury.

Renal ischemia-reperfusion injury (IRI) is one of the causes of acute kidney injury. Annexin A5 (AnxA5), a calcium-dependent cell membrane-binding protein, shows protective effects in various organ IRI models. This study explored the therapeutic effect of exogenous AnxA5 monomer protein on renal IRI and its potential mechanism of action. Different doses of AnxA5 were injected intravenously to treat bilateral renal IRI in SD rats. This model confirmed the protective effects of AnxA5 on kidney structure and function. In vitro, HK-2 cells were subjected to hypoxia for 12h, followed by restoration of normal oxygen supply to simulate IRI. In vitro experiments demonstrated the mechanism of action of AnxA5 by measuring cellular activity and permeability. A comparison of the mutant AnxA5 protein M23 and the application of a calcium-free culture medium further validated the protective effect of AnxA5 by forming a network structure. Exogenous AnxA5 monomers prevented renal IRI by binding to the damaged renal tubular epithelial cell membrane, forming a two-dimensional network structure to maintain cell membrane integrity, and ultimately prevent cell death.

#1806 Cycling is safe – effect of intradialytic cycle ergometry on cerebral oxygenation and cognitive function – a pilot study

Abstract Background and Aims Patients on chronic hemodialysis benefit from intradialytic exercise with improvements in endurance, muscle strength and health-related quality of life. It is not known whether the increased oxygen demand during intradialytic exercise negatively affects cerebral oxygenation and cerebral function. The aim of the study was to assess the risk of cerebral undersupply by measuring cerebral oxygenation, perfusion and cognitive function during and after intradialytic ergometer training. Method Twelve patience on maintenance hemodialysis (HD) trice weekly were included in the study. In an initial ramp test, using bed cycle ergometer, we first determined the maximum physical strength (Pmax) at the level of exhaustion (HD A). Then, one hour after start of a second HD (HD B), patients performed 40%, 50% and 60% of Pmax for 6 min. Pulmonary function tests, blood volume (BVM), cardiac output (by electrical cardiometry), regional cerebral oxygen saturation (rSO2) (by near-infrared spectroscopy) and cerebral blood flow (CBF, by Doppler sonography) were measured. The relative changes in rSO2, CBF and hematocrit were used to calculate cerebral oxygen supply (DO2). Cognitive tests (Stroop, Trail Making and Mini Addenbrookes Cognitive Examination Test) were performed before and after HD sessions with and, as controls, without ergometry (HD-C). Results Median age was 68 (42-85) years, 9/12 were male, complete data set was obtained in 10 patients. During step test exercise (HD B), at the highest exercise level (according to Borg (1-10) 6.75 ± 2.9), rSO2 increased (+6 ± 9%, p=0.034) without a significant change in CBF. In the meantime, relative blood volume decreased during ergometry (-5.8 ± 2.73%; p=0.002), causing a temporary increase of hematocrit. Despite a small decrease in CBF in 3 patients, the mean change of rSO2, CBF and hematocrit always had a positive trend in all patients, as a surrogate of stable cerebral oxygen supply (Table 1). In comparative cognitive tests (B vs. C), we observed no significant changes in cognitive functions. Conclusion In this pilot study, intradialytic bed-cycle ergometry during the first hour of HD for &amp;lt;20 min at 40-60% of patients’ individual maximum intensity had no negative effects on cerebral oxygenation and function. Specific studies testing the safety intradialytic exercise with different conditions, such as increasing intensity or duration, are needed.

ACUTE MYOCARDIAL INFARCTION DURING VRD CHEMOTHERAPY IN A PATIENT WITH MULTIPLE MYELOMA: A CLINICAL CASE

Acute myocardial infarction is a critical condition associated with significant morbidity and mortality rates. Myocardial infarction-related acute myocardial injury is characterized by a rapid elevation and subsequent decline in cardiac troponin concentration. According to the relevant data patients with multiple myeloma are in a high-risk category for venous and arterial thrombosis. Therefore, the incidence of cardiovascular complications, which include myocardial infarction, in these patients is higher than in the general population. The development of metaplastic anemia further compounds this risk by diminishing myocardial oxygen supply. Moreover, chemotherapy for oncohematological diseases carries the potential for cardiotoxic cardiovascular complications. Immunomodulator drugs like Thalidomide and Lenalidomide, frequently utilized in multiple myeloma treatment, have been associated with Lenalidomide-induced myocardial infarction—a prevalent adverse effect. The use of proteasome inhibitors such as Bortezomib and Carfilzomib poses an increased risk for myocardial infarction development. This clinical case presents an instance of acute myocardial infarction in a multiple myeloma patient during low cumulative chemotherapy dosage, comprising Lenalidomide and Bortezomib. It underscores the necessity for enhanced clinical, instrumental, and laboratory monitoring before each specific chemotherapy course in high-risk multiple myeloma patients. Such monitoring facilitates the early detection of chemotherapy-induced cardiotoxic effects, allowing for timely intervention and management.

Numerical analysis and industrial practice of single-flow post-combustion oxygen lance with high oxygen supply intensity

The oxygen supply process is a vital operation in converter steelmaking, which is to inject oxygen and kinetic energy into the liquid bath with an oxygen lance. Herein, a single-flow post-combustion oxygen lance (SF-PCL) with four primary holes and six secondary holes was designed to increase the oxygen supply intensity of a 60-ton converter in a steel plant. The attenuation and coalescence behaviors of supersonic jets for the conventional four-hole oxygen lance (COL) and the newly designed SF-PCL were studied by numerical simulation. And then, their metallurgical effects were verified by industrial practice. The simulation results indicated that the SF-PCL effectively suppresses the attenuation and coalescence of supersonic jets as well as simultaneously increases both the impact area and penetration depth. In industrial practice, compared with the COL, the newly designed SF-PCL increases the oxygen supply intensity from the original 4.89 m3 (t·min)−1 to 5.43 m3 (t·min)−1, rises the dephosphorization rate by 1.4%, shortens the blowing time by 34 s, reduces the ferrous charges consumption by 7 kg t−1 and decreases the total iron content in final slag by 0.85%.

Limning of HIF-2 and HIF-3 in the Tumor Microenvironment: Developing Concepts for the Treatment of Hypoxic Cancer.

Hypoxia, characterized by insufficient oxygen supply to tissues, is a significant factor in tumor growth and resistance to treatment. The hypoxia-inducible factor (HIF) signaling pathway is activated when oxygen levels decline, influencing cell activities and promoting tumor progression. HIF-1α and HIF-2α are the main targets for therapeutic intervention in tumors. Nevertheless, the significance of HIF-2α is often overlooked. This review examines the physiological role of HIF-2α in tumor growth and its involvement in tumor growth. HIFs, composed of hypoxia-responsive α and oxygeninsensitive β subunits, play a crucial role in controlling gene expression in both normal and solid tumor tissues under low oxygen levels. HIF-3α, formerly considered a detrimental modulator of HIF-regulated genes, exerts a transcriptional regulatory role by inhibiting gene expression through competition with HIF-1α and HIF-2α for binding to transcriptional sites in target genes under hypoxia. Recent research indicates that various HIF-3 variants exhibit distinct and potentially contrasting functionalities. Hypoxia often occurs during the initiation and progression of cancer formation. Recent research has discovered that HIF-2α, also known as endothelial PAS domain protein 1, has a significant impact on tumors. HIF-2α is a significant cancer-causing gene and a crucial predictor of prognosis in non-small cell lung cancer. However, due to limited research investigating the relationship between HIF-2α and small-cell lung cancer, it is not possible to reach a definitive conclusion. HIF-2α plays a vital function in cancer by preserving the stemness of cancer cells. This review provides a comprehensive overview of HIF-2 and the role of HIF-3 in various cancer-related processes, as well as its potential as a targeted therapeutic approach.

Ninerafaxstat in the Treatment of Cardiometabolic Disease: Shifting Metabolic Paradigms.

Cardiovascular disease (CVD) refers to a wide array of conditions that damage the heart muscle and impede its ability to effectively circulate blood throughout the body. In damaged or pathological states, the heart muscle might not function as effectively as it would have had there been no insult to it. Understanding this, certain CVDs can put the heart in a "metabolic disadvantage"-a state in which it cannot synthesize energy stores, in the form of adenosine triphosphate (ATP), as efficiently as it was once able to do. While the heart typically uses fatty acids for its ATP synthesis, the metabolic processes required to do so consume more oxygen per mole than the processes required to convert glucose (or carbohydrates) to ATP. In conditions when oxygen demand outweighs supply-such as angina, heart failure, and certain inherited CVDs-the myocardium can more efficiently run via glucose oxidation. Despite this knowledge, there are no currently approved therapeutics or interventions that encourage this "metabolic shift" in the myocardial cells. Currently in phase II clinical trials, however, is a novel medication called ninerafaxstat. This novel drug is a partial inhibitor of fatty acid oxidation and thus pushes the heart to convert glucose (instead of fatty acids) to ATP-ultimately cutting down on oxygen supply. While still completing clinical trials, ninerafaxstat must undergo further safety and efficacy evaluation before it can be used as a standard of care. If, however, the drug makes it to market, it might offer a unique way to improve both the symptoms and quality of life of the millions of Americans who suffer from CVDs.

Programmable Singlet Oxygen Battery for Automated Photodynamic Therapy Enabled by Pyridone-Pyridine Tautomer Engineering.

The efficacy of photodynamic therapy is hindered by the hypoxic environment in tumors and limited light penetration depth. The singlet oxygen battery (SOB) has emerged as a promising solution, enabling oxygen- and light-independent 1O2 release. However, conventional SOB systems typically exhibit an "always-ON" 1O2 release, leading to potential 1O2 leakage before and after treatment. This not only compromises therapeutic outcomes but also raises substantial biosafety concerns. In this work, we introduce a programmable singlet oxygen battery, engineered to address all the issues discussed above. The concept is illustrated through the development of a tumor-microenvironment-responsive pyridone-pyridine switch, PyAce, which exists in two tautomeric forms: PyAce-0 (pyridine) and PyAce (pyridone) with different 1O2 storage half-lives. In its native state, PyAce remains in the pyridone form, capable of storing 1O2 (t1/2 = 18.5 h). Upon reaching the tumor microenvironment, PyAce is switched to the pyridine form, facilitating rapid and thorough 1O2 release (t1/2 = 16 min), followed by quenched 1O2 release post-therapy. This mechanism ensures suppressed 1O2 production pre- and post-therapy with selective and rapid 1O2 release at the tumor site, maximizing therapeutic efficacy while minimizing side effects. The achieved "OFF-ON-OFF" 1O2 therapy showed high spatiotemporal selectivity and was independent of the oxygen supply and light illumination.

Climate change consequences on the systemic heart of female Octopus maya: oxidative phosphorylation assessment and the antioxidant system.

There is evidence that indicates that temperature modulates the reproduction of the tropical species Octopus maya, through the over- or under-expression of many genes in the brain. If the oxygen supply to the brain depends on the circulatory system, how temperature affects different tissues will begin in the heart, responsible for pumping the oxygen to tissues. The present study examines the impact of heat stress on the mitochondrial function of the systemic heart of adult O. maya. The mitochondrial metabolism and antioxidant defense system were measured in the systemic heart tissue of female organisms acclimated to different temperatures (24, 26, and 30°C). The results show that acclimation temperature affects respiratory State 3 and State 4o (oligomycin-induced) with higher values observed in females acclimated at 26°C. The antioxidant defense system is also affected by acclimation temperature with significant differences observed in superoxide dismutase, glutathione S-transferase activities, and glutathione levels. The results suggest that high temperatures (30°C) could exert physical limitations on the circulatory system through the heart pumping, affecting nutrient and oxygen transport to other tissues, including the brain, which exerts control over the reproductive system. The role of the cardiovascular system in supporting aerobic metabolism in octopus females is discussed.

Thyroid hormone analogues: Promising therapeutic avenues to improve the neurodevelopmental outcomes of intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is a pregnancy complication impairing fetal growth and development. The compromised development is often attributed to disruptions of oxygen and nutrient supply from the placenta, resulting in a number of unfavourable physiological outcomes with impaired brain and organ growth. IUGR is associated with compromised development of both grey and white matter, predisposing the infant to adverse neurodevelopmental outcomes, including long-lasting cognitive and motor difficulties. Cerebral thyroid hormone (TH) signalling, which plays a crucial role in regulating white and grey matter development, is dysregulated in IUGR, potentially contributing to the neurodevelopmental delays associated with this condition. Notably, one of the major TH transporters, monocarboxylate transporter-8 (MCT8), is deficient in the fetal IUGR brain. Currently, no effective treatment to prevent or reverse IUGR exists. Management strategies involve close antenatal monitoring, management of maternal risk factors if present and early delivery if IUGR is found to be severe or worsening in utero. The overall goal is to determine the most appropriate time for delivery, balancing the risks of preterm birth with further fetal compromise due to IUGR. Drug candidates have shown either adverse effects or little to no benefits in this vulnerable population, urging further preclinical and clinical investigation to establish effective therapies. In this review, we discuss the major neuropathology of IUGR driven by uteroplacental insufficiency and the concomitant long-term neurobehavioural impairments in individuals born IUGR. Importantly, we review the existing clinical and preclinical literature on cerebral TH signalling deficits, particularly the impaired expression of MCT8 and their correlation with IUGR. Lastly, we discuss the current evidence on MCT8-independent TH analogues which mimic the brain actions of THs by being metabolised in a similar manner as promising, albeit underappreciated approaches to promote grey and white matter development and improve the neurobehavioural outcomes following IUGR.

Stem Cell Angiogenesis in Myocardial Infraction Treatment: Efficacy and Future Directions

Stem Cell Angiogenesis in Myocardial Infraction Treatment: Efficacy and Future Directions

Examining the Influence of Cognitive Load and Environmental Conditions on Autonomic Nervous System Response in Military Aircrew: A Hypoxia-Normoxia Study.

Executing flight operations demand that military personnel continuously perform tasks that utilize low- and high-order cognitive functions. The autonomic nervous system (ANS) is crucial for regulating the supply of oxygen (O2) to the brain, but it is unclear how sustained cognitive loads of different complexities may affect this regulation. Therefore, in the current study, ANS responses to low and high cognitive loads in hypoxic and normoxic conditions were evaluated. The present analysis used data from a previously conducted, two-factor experimental design. Healthy subjects (n = 24) aged 19 to 45 years and located near Fort Novosel, AL, participated in the parent study. Over two, 2-h trials, subjects were exposed to hypoxic (14.0% O2) and normoxic (21.0% O2) air while simultaneously performing one, 15-min and one, 10-min simulation incorporating low- and high-cognitive aviation-related tasks, respectively. The tests were alternated across five, 27-min epochs; however, only epochs 2 through 4 were used in the analyses. Heart rate (HR), HR variability (HRV), and arterial O2 saturation were continuously measured using the Warfighter MonitorTM (Tiger Tech Solutions, Inc., Miami, FL, USA), a previously validated armband device equipped with electrocardiographic and pulse oximetry capabilities. Analysis of variance (ANOVA) regression models were performed to compare ANS responses between the low- and high-cognitive-load assessments under hypoxic and normoxic conditions. Pairwise comparisons corrected for familywise error were performed using Tukey's test within and between high and low cognitive loads under each environmental condition. Across epochs 2 through 4, in both the hypoxic condition and the normoxic condition, the high-cognitive-load assessment (MATB-II) elicited heightened ANS activity, reflected by increased HR (+2.4 ± 6.9 bpm) and decreased HRV (-rMSSD: -0.4 ± 2.7 ms and SDNN: -13.6 ± 14.6 ms). Conversely, low cognitive load (ADVT) induced an improvement in ANS activity, with reduced HR (-2.6 ± 6.3 bpm) and increased HRV (rMSSD: +1.8 ± 6.0 ms and SDNN: vs. +0.7 ± 6.3 ms). Similar observations were found for the normoxic condition, albeit to a lower degree. These within-group ANS responses were significantly different between high and low cognitive loads (HR: +5.0 bpm, 95% CI: 2.1, 7.9, p < 0.0001; rMSSD: -2.2 ms, 95% CI: -4.2, -0.2, p = 0.03; SDNN: -14.3 ms, 95% CI: -18.4, -10.1, p < 0.0001) under the hypoxic condition. For normoxia, significant differences in ANS response were only observed for HR (+4.3 bpm, 95% CI: 1.2, 7.4, p = 0.002). Lastly, only high cognitive loads elicited significant differences between hypoxic and normoxic conditions but just for SDNN (-13.3 ms, 95% CI, -17.5, -8.9, p < 0.0001). Our study observations suggest that compared to low cognitive loads, performing high-cognitive-load tasks significantly alters ANS activity, especially under hypoxic conditions. Accounting for this response is critical, as military personnel during flight operations sustain exposure to high cognitive loads of unpredictable duration and frequency. Additionally, this is likely compounded by the increased ANS activity consequent to pre-flight activities and anticipation of combat-related outcomes.

Exposure to fine particulate matter 2.5 from wood combustion smoke causes vascular changes in placenta and reduce fetal size

During gestation, maternal blood flow to the umbilical cord and placenta increases, facilitating efficient nutrient absorption, waste elimination, and effective gas exchange for the developing fetus. However, the effects of exposure to wood smoke during this period on these processes are unknown. We hypothesize that exposure to PM2.5, primarily sourced from wood combustion for home heating, affects placental vascular morphophysiology and fetal size. We used exposure chambers that received either filtered or unfiltered air. Female rats were exposed to PM2.5 during pre-gestational and/or gestational stages. Twenty-one days post-fertilization, placentas were collected via cesarean section. In these placentas, oxygen diffusion capacity was measured, and the expression of angiogenic factors was analyzed using qPCR and immunohistochemistry. In groups exposed to PM2.5 during pre-gestational and/or gestational stages, a decrease in fetal weight, crown-rump length, theoretical and specific diffusion capacity, and an increase in HIF-1α expression were observed. In groups exposed exclusively to PM2.5 during the pre-gestational stage, there was an increase in the expression of placental genes Flt-1, Kdr, and PIGF. Additionally, in the placental labyrinth region, the expression of angiogenic factors was elevated. Changes in angiogenesis and angiogenic factors reflect adaptations to hypoxia, impacting fetal growth and oxygen supply. In conclusion, this study demonstrates that exposure to PM2.5, emitted from wood smoke, in both pre-gestational and gestational stages, affects fetal development and placental health. This underscores the importance of addressing air pollution in areas with high levels of wood smoke, which poses a significant health risk to pregnant women and their fetuses.

A self‐regulated phototheranostic nanosystem with single wavelength‐triggered energy switching and oxygen supply for multimodal synergistic therapy of bacterial biofilm infections

AbstractThe exploration of antibiotic‐independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention. However, efficient eradication of bacterial biofilms remains a challenge. Herein, a self‐regulated phototheranostic nanosystem with single wavelength‐triggered photothermal therapy (PTT)/photodynamic therapy (PDT) transformation and oxygen supply for multimodal synergistic therapy of bacterial biofilm infections is presented. This approach combines a eutectic mixture of natural phase‐change materials (PCMs) and an aggregation‐induced emission (AIE) phototheranostic agent TPA‐ICN to form colloidally stable nanopartcicles (i.e. AIE@PCM NPs). The reversible solid−liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA‐ICN, enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs. Additionally, oxygen‐carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT. The nanosystem exhibits outstanding therapeutic efficacy against bacterial biofilms both in vitro and in vivo, with an antibacterial efficiency of 99.99%. This study utilizes a self‐regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat‐triggered oxygen release, holding great promise in the safe and efficient treatment of bacterial biofilm infections.

Nanogalvanic Cells Release Highly Reactive Electrons in Tumors to Effectively Eliminate Tumors.

External stimuli triggering chemical reactions in cancer cells to generate highly reactive chemical species are very appealing for cancer therapy, in which external irradiation activating sensitizers to transfer energy or electrons to surrounding oxygen or other molecules is critical for generating cytotoxic reactive species. However, poor light penetration into tissue, low activity of sensitizers, and reliance on oxygen supply restrict the generation of cytotoxic chemical species in hypoxic tumors, which lowers the therapeutic efficacy. Here, we present galvanic cell nanomaterials that can directly release highly reactive electrons in tumors without external irradiation or photosensitizers. The released reactive electrons directly react with surrounding biomolecules such as proteins and DNA within tumors to destroy them or react with other surrounding (bio)molecules to yield cytotoxic chemical species to eliminate tumors independent of oxygen. Administering these nanogalvanic cells to mice results in almost complete remission of subcutaneous solid tumors and deep metastatic tumors. The results demonstrate that this strategy can further arouse an immune response even in a hypoxic environment. This method offers a promising approach to effectively eliminate tumors, similar to photodynamic therapy, but does not require oxygen or irradiation to activate photosensitizers. This article is protected by copyright. All rights reserved.

Infection-Free and Enhanced Wound Healing Potential of Alginate Gels Incorporating Silver and Tannylated Calcium Peroxide Nanoparticles.

The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen supply has been validated as a therapeutic approach to improve and speed up wound healing. Moreover, the local implications of antimicrobial agents (such as silver-based nano-compounds) significantly support the normal healing process, by combating bacterial contamination and colonization. In this study, silver (S) and tannylated calcium peroxide (CaO2@TA) nanoparticles were obtained by adapted microfluidic and precipitation synthesis methods, respectively. After complementary physicochemical evaluation, both types of nanoparticles were loaded in (Alg) alginate-based gels that were further evaluated as possible dressings for wound healing. The obtained composites showed a porous structure and uniform distribution of nanoparticles through the polymeric matrix (evidenced by spectrophotometric analysis and electron microscopy studies), together with a good swelling capacity. The as-proposed gel dressings exhibited a constant and suitable concentration of released oxygen, as shown for up to eight hours (UV-Vis investigation). The biofilm modulation data indicated a synergistic antimicrobial effect between silver and tannylated calcium peroxide nanoparticles, with a prominent inhibitory action against the Gram-positive bacterial biofilm after 48 h. Beneficial effects in the human keratinocytes cultured in contact with the obtained materials were demonstrated by the performed tests, such as MTT, LDH, and NO.