Arterial Saturation Research Articles

Respiratory Syncytial Virus and Influenza Infections in Children in Ulaanbaatar, Mongolia, 2015-2021.

Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.

Influence of hemoglobin-O2 affnity on aerobic capacity in deer mice

High-altitude hypoxia can constrain tissue O2 supply, and several high-altitude populations and species have evolved adaptations to overcome this challenge. Evolved increases in hemoglobin-O2 (Hb-O2) affnity are pervasive across high-altitude taxa, but the influence of such increases on aerobic capacity (maximal O2 consumption) in hypoxia remains contentious. The influence of Hb-O2 affnity on aerobic capacity in hypoxia could vary depending on other traits in the O2 transport pathway, but this possibility is poorly understood. We examined this issue in deer mice ( Peromyscus maniculatus), which is found from sea level to &gt;4300m altitude in the Rocky Mountains. Mice from populations native to high altitude and low altitude were born and raised to adulthood in captivity. Low-altitude mice (n=14) were acclimated to warm (25°C) normoxia, and high-altitude mice (n=14) were acclimated to cold (5°C) hypoxia (~12 kPa O2) for 6 weeks, creating two groups with very different capacities for O2 transport in hypoxia. Aerobic capacity for thermogenesis (VO2max) was then measured in hypoxia after each of three pharmacological treatments to manipulate Hb-O2 affnity: saline (control); efaproxiral, a negative allosteric regulator that decreases Hb-O2 affnity; and sodium cyanate, which covalently modifies Hb and increases Hb-O2 affnity. In control conditions, high-altitude mice had higher VO2max and arterial O2 saturation (SaO2) in hypoxia and higher Hb-O2 affnity (lower P50) than low-altitude mice. Efaproxiral reduced SaO2 and led to similar decreases in VO2max in both populations. Sodium cyanate increased SaO2 in hypoxia in both populations. However, this was only associated with an increase in VO2max in 7 of 14 high-altitude mice and 4 of 14 low-altitude mice. Our results suggest that Hb-O2 affnity may be optimal for aerobic capacity in hypoxia in high-altitude mice, and that reductions in Hb-O2 affnity reduce performance. Supported by NSERC of Canada. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute moderate normobaric hypoxia does not modify circulating thyroid hormone concentrations induced by 1 h of head-out cold-water immersion.

This study tested the hypothesis that acute moderate normobaric hypoxia augments circulating thyroid hormone concentrations during and following 1 h of cold head-out water immersion (HOWI), compared with when cold HOWI is completed during normobaric normoxia. In a randomized crossover single-blind design, 12 healthy adults (27 ± 2 yr, 2 women) completed 1 h of cold (22.0 ± 0.1°C) HOWI breathing either normobaric normoxia ([Formula: see text] = 0.21) or normobaric hypoxia ([Formula: see text] = 0.14). Free and total thyroxine (T3) and triiodothyronine (T4), and thyroid-stimulating hormone (TSH) concentrations were measured in venous blood samples obtained before (baseline), during (15-, 30-, and 60 min), and 15 min following HOWI (post-), and were corrected for changes in plasma volume. Arterial oxyhemoglobin saturation and core (rectal) temperature were measured continuously. Arterial oxyhemoglobin saturation was lower during hypoxia (90 ± 3%) compared with normoxia (98 ± 1%, P < 0.001). Core temperature fell from baseline (normoxia: 37.2 ± 0.4°C, hypoxia: 37.2 ± 0.4°C) to post-cold HOWI (normoxia: 36.4 ± 0.5°C, hypoxia: 36.3 ± 0.5°C, P < 0.001) in both conditions but did not change differently between conditions (condition × time: P = 0.552). Circulating TSH, total T3, free T4, total T3, and free T4 concentrations demonstrated significant main effects of time (all P ≤ 0.024), but these changes did not differ between normoxic and hypoxic conditions (condition × time: all P ≥ 0.163). These data indicate that acute moderate normobaric hypoxia does not modify the circulating thyroid hormone response during 1 h of cold HOWI.NEW & NOTEWORTHY Acute head-out cold (22°C) water immersion (HOWI) decreased core temperature and increased thermogenesis. This thermogenic response was paralleled by the activation of the hypothalamic-pituitary-thyroid axis, as evidenced by changes in thyroid hormones. However, cold HOWI in combination with moderate normobaric hypoxia did not modify the thermogenic nor the circulating thyroid hormone response. This finding suggests that hypoxia-induced alterations in thyroid hormone concentrations are unlikely to acutely contribute to adaptations resulting from repeated cold-water exposures.

Cardiorespiratory Responses to Acute Intermittent Hypoxia in Humans With Chronic Spinal Cord Injury.

Brief exposure to repeated episodes of low inspired oxygen, or acute intermittent hypoxia (AIH), is a promising therapeutic modality to improve motor function after chronic, incomplete spinal cord injury (SCI). Although therapeutic AIH is under extensive investigation in persons with SCI, limited data are available concerning cardiorespiratory responses during and after AIH exposure despite implications for AIH safety and tolerability. Thus, we recorded immediate (during treatment) and enduring (up to 30 min post-treatment) cardiorespiratory responses to AIH in 19 participants with chronic SCI (>1 year post-injury; injury levels C1 to T6; American Spinal Injury Association Impairment Scale A to D; mean age = 33.8 ± 14.1 years; 18 males). Participants completed a single AIH (15, 60-sec episodes, inspired O2 ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O2 ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% (p < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min (p = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm (p = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, n = 11), whereas others responded minimally (<0.20 L/min/%, n = 8). Apneas occurred frequently during AIH and/or Sham protocols in multiple participants. All participants completed AIH treatment without difficulty. No significant changes in ventilation, heart rate, or arterial blood pressure were found 30 min post-AIH p > 0.05). In conclusion, therapeutic AIH is well tolerated, elicits variable chemoreflex activation, and does not cause persistent changes in cardiorespiratory control/function 30 min post-treatment in persons with chronic SCI.

Validation of retinal oximetry vessel selection using fluorescein angiography in patients with optic disc drusen

Retinal oximetry could provide insights into the pathophysiology of optic nerve disease, including optic disc drusen (ODD). Vessel selection for oximetry analysis is based on morphological characteristics of arterioles and venules and supported by an overlay of estimated blood oxygen saturations. The purpose of this cross-sectional study was to determine the validity of this vessel selection procedure by comparing it with vessel selection supported by video fluorescein angiography (FA).The study included 36 eyes of 36 patients with ODD who underwent retinal oximetry (Oxymap retinal oximeter T1) followed by FA (Heidelberg Spectralis). Two trained graders selected vessel segments in a pre-defined measurement area around the optic disc. One of these graders additionally performed the vessel segment selection with the support of FA images. When performed by the same grader, FA-supported and non-FA-supported vessel selection did not lead to significant differences in total vessel segment length, estimated oxygen saturations or vessel diameters (all p > 0.05). Inter-grader differences were found for arterial and venous segment lengths and arterial saturation (p < 0.05). A similar tendency was found for the arteriovenous saturation difference (p = 0.10). In conclusion, identifying vessel segments for retinal oximetry analysis based on vessel morphology and supported by a color-coded saturation overlay appears to be a valid method without the need for invasive angiography. A numerically small inter-grader variation may influence oximetry results. Further studies of retinal oximetry in ODD are warranted.

83 Automated PDMS Engraving and Assembly of a Prototype Microfluidic Artificial Lung

OBJECTIVES/GOALS: We report an automated manufacturing system, and a series of cylindrical multi-layer microfluidic artificial lungs manufactured with the system and tested for fluidic fidelity and function. METHODS/STUDY POPULATION: A Roll-to-Roll (R2R) system to engrave multiple-layer devices was assembled. A 100 um-thick silicone sheet passes through an embedded CO2 laser engraver, which creates patterns of any geometry on the surface. The sheet is plasma-activated to create an irreversible bond, and rerolled into a processed device. Unlike typical applications of R2R, this process is synchronized to achieve consistent radial positioning. This allows the fluidics in the device to be accessed without being unwrapped. The result is a cylindrical core surrounded by many layers of microfluidic channels that can be accessed through the side of the device or through fluidic vias. This core is cut to expose the microfluidic layers, and then installed into a housing which routes the fluids into their respective microfluidic flow paths. RESULTS/ANTICIPATED RESULTS: To demonstrate the capabilities of the R2R manufacturing system, this method was used to manufacture multi-layer microfluidic artificial lungs (µALs). Gas and blood flow channels are engraved in alternating layers and routed orthogonally. The close proximity of gas and blood separated by gas-permeable PDMS permits CO2 and O2 exchange. Three µALs were successfully manufactured. Their flow paths were visualized using dyed water and checked for leaks. Then they were evaluated using water for pressure drop and CO2 gas-exchange. The top performing device had 15 alternating blood and gas layers. Test with whole blood demonstrated oxygenation from venous (70%) saturation levels to arterial (95%) saturation levels at a flow rate of 3 ml/min. DISCUSSION/SIGNIFICANCE: The ability to cost-effectively produce high surface area microfluidic devices would bring many small-scale technologies from the realm of research to clinical and commercial applications. In particular, most microfluidic artificial lungs only have small rated flows due to a lack of manufacturing processes able to create high surface area devices.

Effect of lower body negative pressure on cardiac and cerebral function in postural orthostatic tachycardia syndrome: A pilot MRI assessment.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of -25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2 ) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2 ; susceptometry-based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: -0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function.

Arterial oxygen desaturation during moderate hypoxia hinders sensorimotor performance.

Moderate hypoxia may impact cognitive and sensorimotor performance prior to self-recognized impairments. Therefore, rapid and objective assessment tools to identify people at risk of impaired function during moderate hypoxia is needed. Test the hypothesis that reductions in arterial oxygen saturation during moderate normobaric hypoxia (FiO2 = 14%) decreases gamified sensorimotor performance as measured by alterations of motor acuity. Following three consecutive days of practice, thirty healthy adults (25 ± 5 y, 10 females) completed three bouts of the tablet-based gamified assessment (Statespace Labs, Inc.) of motor acuity at Baseline and 60 and 90 min after exposure to 13.8 ± 0.2% (hypoxia) and 20.1 ± 0.4% (normoxia) oxygen. The gamified assessment involved moving the tablet to aim and shoot at targets. Both conditions were completed on the same day and were administered in a single-blind, block randomized manner. Performance metrics included shot time and shot variability. Arterial oxyhemoglobin saturation estimated via forehead pulse oximetry (SpO2). Data were analyzed using linear mixed effects models. Compared to normoxia (99±1%), SpO2 was lower (p<0.001) at 60 (89±3%) and 90 (90±2%) min of hypoxia. Shot time was unaffected by decreases in SpO2 (0.012, p = 0.19). Nor was shot time affected by the interaction between SpO2 decrease and baseline performance (0.006, p = 0.46). Shot variability was greater (i.e., less precision, worse performance) with decreases in SpO2 (0.023, p = 0.02) and depended on the interaction between SpO2 decrease and baseline performance (0.029, p< 0.01). Decreases in SpO2 during moderate hypoxic exposure hinders sensorimotor performance via decreased motor acuity, i.e., greater variability (less precision) with no change in speed with differing decreases in SpO2. Thus, personnel who are exposed to moderate hypoxia and have greater decreases in SpO2 exhibit lower motor acuity, i.e., less precise movements even though decision time and movement speed are unaffected.

Respiratory Effects of Continuous Positive Airway Pressure Administered during Recovery from General Anesthesia in Brachycephalic Dogs.

This study aimed to evaluate the benefits of applying 5 cmH2O of CPAP using a pediatric helmet during the recovery phase from general anesthesia in brachycephalic dogs. Brachycephalic dogs undergoing various surgical procedures were included in this study, and a total of 64 subjects were randomly assigned to receive either standard oxygen supplementation (NO-CPAP group) or oxygen supplementation combined with CPAP (CPAP group). This study evaluated arterial blood pH, blood gas partial pressures of O2 and CO2, arterial blood O2 saturation, and related parameters during recovery. The dogs were monitored, and helmet tolerance was assessed using predefined criteria. Of the initially assessed 69 dogs, 64 were enrolled: 32 in the CPAP group and 32 in the NO-CPAP group. Fifteen dogs in the NO-CPAP group were excluded based on predetermined criteria. The CPAP group showed significant improvements in PaO2, PaO2/FiO2, P(A-a)O2, F-Shunt, and respiratory rate compared with the NO-CPAP group (p < 0.001). The incidence of reintubation and helmet intolerance was higher in the NO-CPAP group (18% and 15.6%, respectively) than in the CPAP group (0%). This study highlights the potential benefits of incorporating CPAP, delivered through a pediatric helmet, in the perioperative management of brachycephalic dogs.

Exercise catheterization in adults post-Fontan with normal and abnormal haemodynamic criteria: Insights into normal Fontan physiology.

The normal (i.e. expected) haemodynamics in adults post-Fontan remain poorly delineated. Moreover, the definitions of elevated exercise pulmonary artery (PA) and PA wedge pressure (PAWP) for this population have not been described. Seventy-two adults post-Fontan undergoing exercise catheterization were categorized into abnormal (Group I, n = 59; defined as resting mean PA ≥14 mmHg and/or PAWP ≥12 mmHg, ΔPAWP/Δsystemic flow [Qs] >2 mmHg/L/min, and/or ΔPA/Δpulmonary flow >3 mmHg/L/min) and normal (Group II, n = 13) haemodynamics. Thirty-nine patients with non-cardiac dyspnoea (NCD) were included as controls. There was no difference in exercise arterial oxygen saturation (87% [81-92] vs. 89% [85-93], p = 0.29), while exercise PA pressure (27 [23-31] vs. 16 [14.5-19.5] mmHg, p < 0.001) and PAWP were higher (21 [18-28] vs. 12 [8-14] mmHg, p < 0.001) in Group I. At peak exercise, Group I had lower heart rate (97 [81-120] vs. 133 [112.5-147.5] bpm, p < 0.001) and Qs response (67.3 [43.8-93.1] vs. 105.9 (82-118.5) % predicted, p < 0.001) than Group II. Exercise superior vena cava pressures were higher (16 [14-22.5] vs. 5.5 [3-7.3] mmHg, p < 0.001) and arterial oxygen saturation lower (89% [85-93] vs. 97% [96-98], p < 0.001) in Group II compared to NCD, while no differences in PAWP, stroke volume index, heart rate, or Qs response were seen. If defined as two standard deviations above mean values for Group II, elevated PAWP and mean PA pressure post-Fontan would correspond to 20.6 mmHg and 25.8 mmHg, respectively. PAWP >20 mmHg and mean PA pressure >25 mmHg could be used to define elevated values during exercise in adults post-Fontan. The major discrepancy in exercise haemodynamics among Group II compared to controls appears to be the degree of systemic venous hypertension and arterial desaturation.

An innovative method to prevent infection when measuring the arterial blood gas SpO2 saturation.

Patients are hospitalized for extended periods, particularly in intensive care units (ICUs). As a result, the saturation probe (pulse oximeter) remains attached for an extended period and microorganisms can grow in the wet environment. If the pulse oximeters are not reprocessed, cross-infection may occur. The literature contains several studies in which gloves were used for the measurement while various SpO2 (peripheral arterial oxygen saturation) measurements were compared with each other. However, such comparisons have yet to be made with the results of arterial blood gas SpO2 measurements by pulse oximeter, considered as the gold standard. The present study aimed to compare arterial blood gas values with the fingertip saturation measurement performed by having adult patients wear gloves of different colors, one after the other, on their fingers and determining the effect of the differently colored gloves (transparent, white, black, light blue) on saturation values. The study was conducted on 54 patients in an ICU. Intra-arterial blood gas SpO2 results were measured. Oxygen saturation was measured while the patient 1. did not wear gloves and 2. sequentially wore a series of gloves of different colors. Paired t-test, correlation analysis, and Bland Altman charts were used to evaluate the results. The mean SpO2% value of the participants' intra-arterial blood gas measurements was 97.76±2.04. The mean SpO2% value obtained from the measurements of the fingers with a transparent glove was 0.43 points lower than the mean SpO2% value of the intra-arterial blood gas measurements (t=0.986, p=0.61). The mean SpO2% value obtained from the measurements of the fingers with a white glove was 0.93 points lower than the mean SpO2% value of the intra-arterial blood gas measurements (t=1.157, p=0.093). Of the measurements performed with a glove, the mean SpO2% value obtained from the measurements of the fingers with a transparent glove was more consistent with the mean SpO2% value of the intra-arterial blood gas measurements than measurement of the fingers without a glove.

ПРОТЕКТИВНОЕ ВЛИЯНИЕ НООКЛЕРИНА И СЛАВИНОРМА НА КАРДИОРЕСПИРАТОРНЫЕ ФУНКЦИИ КРЫС ПРИ ОХЛАЖДЕНИИ В ВОДЕ

Effects of nooclerin (deanol aceglumate) and slavinorm (vascular polypeptide complex) on the breathing and heart rates were compared in Wistar rats in the course of progressive hypothermia. The animals were immersed in water at 9 ± 0.4 °С. The parameters under study were breathing rate (BR), heart rate (HR), rectal temperature (Тr), esophageal temperature (Tes), and arterial saturation (SpO2). In comparison to controls, at the beginning of hypothermia BR in experimental rats was high at lower Tr values. Nooclerin did not change the trend of HR curve dependence on Tr, whereas slavinorm shifted the trend toward high HR values; besides, it more than doubled life duration before the respiratory arrest. This occurred as a result of rats' transition in the state of cold-hypometabolism when the cardiac activity was maintained by slow breathing. The investigation showed that nooclerin and slavinorm are able to preserve the viability of organisms in hypothermic environment. Both drugs enhance and extend the stage of breathing activation at the beginning of cold immersion in the experimental rats in comparison to their controls. Injection of nooclerin and slavinorm mobilizes the defenses of organism and reduces the pathological effects of deep hypothermia.

Clinical, laboratory and morphological comparisons in cellular alteration under conditions of hypoxia

To compare structural changes in tissues with clinical and laboratory parameters and immunohistochemical determination of proteins HIF1α, HIF2α, caspase-3 during cellular alteration under conditions of hypoxia in the liver and kidneys in an experiment on pigs. Laboratory parameters related to the state of gas exchange (decrease in partial pressure of arterial blood oxygen (PaO2), arterial blood saturation, lactate level, kidney function (creatinine, urea) and liver (ALT, AST, bilirubin) in 18 animals were analyzed in comparison with the results of a morphological study. Histological examination evaluated alterative and inflammatory tissue changes of varying severity, and also determined the expression of transcription factors HIF1α and HIF2α and a marker of apoptosis - caspase-3. The ratio between laboratory parameters and structural changes was assessed individually for each animal. In the liver, a statistically significant dependence of the content of HIF2α protein in cells on the severity of dystrophic changes and serum lactate levels was revealed. A statistically significant correlation was shown between an increase in transaminase and bilirubin levels and the severity of alterative changes in liver tissue. However, there was no significant relationship between the number of caspase-3 positive cells and the severity of dystrophic changes. A statistically significant correlation was found between creatinine and urea levels and the severity of alterative changes in kidney tissues. With significant dystrophic changes, a statistically significant dependence of the expression of HIF2α and caspase-3 proteins and a very high correlation of caspase-3 - lactate indicators were revealed. A significant correlation was shown between histological changes in tissues and clinical and laboratory parameters. Severe hypoxia with lactate accumulation directly affects the integrity and function of cells, which manifests itself in structural changes. Based on the results of a comparative study, it can be concluded that the assessment of alterative changes in liver and kidney tissues is important.

Arterial desaturation rate does not influence self-selected knee extension force but alters ventilatory response to progressive hypoxia: A pilot study.

The absolute magnitude and rate of arterial desaturation each independently impair whole-body aerobic exercise. This study examined potential mechanisms underlying the rate-dependent relationship. Utilizing an exercise protocol involving unilateral, intermittent, isometric knee extensions (UIIKE), we provided sufficient reperfusion time between contractions to reduce the accumulation of intramuscular metabolic by-products that typically stimulate muscle afferents. The objective was to create a milieu conducive to accentuating any influence of arterial desaturation rate on muscular fatigue. Eight participants completed four UIIKE sessions, performing one 3 s contraction every 30s at a perceived intensity of 50% MVC for 25 min. Participants voluntarily adjusted their force generation to maintain perceptual effort at 50% MVC without feedback. Reductions in inspired oxygen fraction (FI O2 ) decreased arterial saturation from >98% to 70% with varying rates in three trials: FAST (5.3 ± 1.3 min), MED (11.8 ± 2.7 min), and SLOW (19.9 ± 3.7 min). FI O2 remained at 0.21 during the control trial. Force generation and muscle activation remained at baseline levels throughout UIIKE trials, unaffected by the magnitude or rate of desaturation. Minute ventilation increased with hypoxia (p < 0.05), and faster desaturation rates magnified this response. These findings demonstrate that arterial desaturation magnitude and rate independently affect ventilation, but do not influence fatigue development during UIIKE.

Right Atrial Pressure Higher Than The Pulmonary Artery Saturation: An Ominous Finding At Right Heart Catheterization

Right Atrial Pressure Higher Than The Pulmonary Artery Saturation: An Ominous Finding At Right Heart Catheterization

Effect of hyperbaric chamber on saturation and heart frequency

Introduction: (1) Background: The use of oxygen under pressure greater than atmospheric represents progress that can be measured in terms of importance with the introduction of blood transfusion and antibiotics in therapy. The aim of the research was to determine the impact of using a hyperbaric chamber (HC) on muscle, arterial saturation and heart rate.; (2) Methods: Twelve respondents who engaged in recreational exercise. HC Macy Pan O2 801 was used for oxygen delivery. Muscle saturation was assessed with the IDIAG Moxy device. Arterial saturation was monitored with an Omron OM-35 device, and intraventricular heart rate with a Polar FT2 device. All parameters were monitored before and after HC treatment for 50 min. and constant pressure of 2.5 ATA.; (3) Results: There was a significant increase in saturation in the pectoralis, (+8.99%) p=.038, hamstring (+8.62%) p=.042. In capillary saturation (+1.42%) p=.008. Heart rate was reduced on average by about 8.5 beats p= .003. In the region of the latissimus do not record a statistically significant change in oxygen (+6.64%) p=060, however, numerical differences were determined.; (4) Conclusions: HC is an effective means of achieving positive physiological effects. It needs to be determined whether a higher ATA or duration of treatment gives better effects.

Assessing amyloid plaque burden in aging marmosets and genetically engineered PSEN1 mutation carriers using 11C‐PiB PET

AbstractBackgroundThere is an urgent need to develop novel animal models to investigate the underlying cellular and molecular root causes of the pathogenesis and progression of AD. Our group has worked to establish the common marmoset as the first primate‐specific model of AD to reveal the earliest cellular and molecular events of AD processes and allow charting of AD progression from its inception. For this, we established a colony of outbred marmosets and used genetic engineering techniques to generate marmosets carrying the PSEN1‐C410Y and PSEN1‐A426P mutations that cause early‐onset, familial AD. The present study aims to use PET imaging to access and track the progression of Ab plaque burden non‐invasively and longitudinally in our marmoset models of AD.MethodMarmosets anesthetized with isoflurane delivered via a facemask were placed in a preclinical PET/CT scanner customized with marmoset‐specific beds. Respiratory rate, heart rate, arterial O2 saturation, and rectal temperature were monitored and maintained at normal physiological values. Our PET imaging protocol follows the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The amyloid‐binding 11C‐Pittsburgh Compound B (11C‐PiB) was delivered intravenously in doses varying from 18.5 – 185 MBq (0.5 – 5 mCi). A 90‐min dynamic acquisition was performed immediately following the radiotracer injection, followed by a 3D CT scan acquired at 200 µm isotropic resolution. After the PET/CT neuroimaging scan, the marmosets were recovered from anesthesia and returned to their home cages.ResultWe observed positive 11C‐PiB binding and retention in the brains of aging outbred marmosets and in marmosets harboring PSEN1 mutations. Significant 11C‐PiB retention was observed in the cortex and white matter tracts. The areas with the highest 11C‐PiB retention were the lateral frontal cortex, anterior cingulate cortex, and temporal lobe regions.ConclusionThis study demonstrates using 11C‐PiB to track Ab plaque burden in the brains of aging marmosets and marmosets harboring PSEN1 mutations. As observed in human patients of AD, the amount of 11C‐PiB bound (measured in SUV and SUVR units) varied from animal to animal, and we are currently performing group analysis to investigate the dependence of 11C‐PiB retention on age and sex. This research was funded by NIH/NIA grants R24AG073190 and U19AG074866.

Assessing amyloid plaque burden in aging marmosets and genetically engineered PSEN1 mutation carriers using 11C‐PiB PET

AbstractBackgroundThere is an urgent need to develop novel animal models to investigate the underlying cellular and molecular root causes of the pathogenesis and progression of AD. Our group has worked to establish the common marmoset as the first primate‐specific model of AD to reveal the earliest cellular and molecular events of AD processes and allow charting of AD progression from its inception. For this, we established a colony of outbred marmosets and used genetic engineering techniques to generate marmosets carrying the PSEN1‐C410Y and PSEN1‐A426P mutations that cause early‐onset, familial AD. The present study aims to use PET imaging to access and track the progression of Ab plaque burden non‐invasively and longitudinally in our marmoset models of AD.MethodMarmosets anesthetized with isoflurane delivered via a facemask were placed in a preclinical PET/CT scanner customized with marmoset‐specific beds. Respiratory rate, heart rate, arterial O2 saturation, and rectal temperature were monitored and maintained at normal physiological values. Our PET imaging protocol follows the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The amyloid‐binding 11C‐Pittsburgh Compound B (11C‐PiB) was delivered intravenously in doses varying from 18.5 – 185 MBq (0.5 – 5 mCi). A 90‐min dynamic acquisition was performed immediately following the radiotracer injection, followed by a 3D CT scan acquired at 200 µm isotropic resolution. After the PET/CT neuroimaging scan, the marmosets were recovered from anesthesia and returned to their home cages.ResultWe observed positive 11C‐PiB binding and retention in the brains of aging outbred marmosets and in marmosets harboring PSEN1 mutations. Significant 11C‐PiB retention was observed in the cortex and white matter tracts. The areas with the highest 11C‐PiB retention were the lateral frontal cortex, anterior cingulate cortex, and temporal lobe regions.ConclusionThis study demonstrates using 11C‐PiB to track Ab plaque burden in the brains of aging marmosets and marmosets harboring PSEN1 mutations. As observed in human patients of AD, the amount of 11C‐PiB bound (measured in SUV and SUVR units) varied from animal to animal, and we are currently performing group analysis to investigate the dependence of 11C‐PiB retention on age and sex.This research was funded by NIH/NIA grants R24AG073190 and U19AG074866.

Assessment of Neurocognitive Functioning in Sickle Cell Disease and Thalassemia and the Association with Silent Cerebral Infarcts and Cerebral Hemodynamics and Oxygen Metabolism

Introduction Neurocognitive impairment is a significant problem in patients with sickle cell disease (SCD), affecting various life domains such as academic achievement, career progress, and general life quality. The cause of this impairment is not yet fully understood, however, it has been linked to silent cerebral infarcts (SCIs) and irregularities in blood perfusion and oxygenation, particularly in children with SCD. Previous research has identified cognitive deficits in adults with SCD, but the relationship with SCIs has not been thoroughly explored in this age group. This study aimed to examine the neurocognitive functioning among adult patients with three types of inherited chronic anemia (severe SCD, mild SCD, and thalassemia) and healthy controls. Additionally, we investigated potential associations of neurocognitive performance with cerebral perfusion and oxygenation, and SCIs. Methods This study included 70 severe SCD patients (60 HbSS, 10 HbSβ 0), 22 mild SCD patients (14 HbSC, 8 HbSβ +), 16 thalassemia patients (6 NTDT, 10 TDT), and 29 healthy controls. We assessed neurocognitive functioning through eight tasks divided into seven neurocognitive domains such as attention, processing speed, nonverbal IQ, working memory, verbal learning, visual memory, and fine motor dexterity. Each task score was standardized using published norm data, converted into Z-scores, and used to compute the mean Z-score per domain. SCIs were assessed and segmented using FLAIR MRI scans. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were derived using time-encoded pseudo-continuous arterial spin labeling (te-pCASL) and T 2-relaxation-under-spin-tagging (TRUST) techniques, respectively. Cerebral metabolic rate of oxygen (CMRO 2) was calculated from the CBF, OEF and oxygen content (calculated from hemoglobin and arterial saturation). One-sample t-tests or one-sample Wilcoxon-signed rank tests were used to compare the seven neurocognitive domains of each group with normative test data and ANOVA was used to compare these domains between participant groups. Independent-sample t-tests or Mann-Whitney U tests were used to compare the neurocognitive domains between patients with and without SCIs. Lastly, correlation analyses explored the relationships between the neurocognitive domains and SCI volume, CBF, OEF, and CMRO 2. Results In the severe SCD group, only processing speed and fine motor dexterity were significantly impaired after adjusting for multiple comparisons (Table 1 &amp; Figure 1). Mild SCD patients exhibited lower scores in processing speed, working memory, and fine motor dexterity compared to the norms. In contrast, after adjustment for multiple comparisons, thalassemia patients and healthy controls only showed significantly lower scores in fine motor dexterity (Table 1). When comparing groups, SCD patients had significantly slower processing speed compared to thalassemia patients and healthy controls. Surprisingly, SCD patients without SCIs exhibited poorer fine motor dexterity than those with SCIs (p=0.03), while no such associations were identified in other groups. Finally, no associations were found between the neurocognitive domains and SCI volumes, CBF, OEF and CMRO 2. Conclusion Our results show slower processing speed in SCD patients compared to thalassemia patients and healthy controls, aligning with previous studies. However, unlike previous research, we did not find additional neurocognitive deficits in SCD patients. This could be due to variations in patient selection, environmental factors, socioeconomic status, or recent enhancements in SCD treatment approaches, such as the early administration of hydroxyurea and/or blood transfusion. Interestingly, all groups showed diminished fine motor dexterity, potentially due to the ongoing digital transition. A key observation from this study was the lack of association between neurocognitive performance and SCIs, hemodynamics, and oxygen metabolism, suggesting that SCIs and oxygenation might not be the only factors contributing to impaired processing speed. Our results suggest that recent developments in medical treatments could have improved the neurocognitive function of SCD patients residing in Western countries. However, concerning the domain of processing speed, further studies are required to investigate other SCD-related factors that might influence this particular area.

Efficacy of intravenous iron therapy compared to usual treatment in iron deficient adult cyanotic congenital heart disease patients for improvement in clinical outcomes at three months

Abstract Background Iron deficiency is frequent in CCHD patients and is associated with poorer outcomes. Patients with iron deficiency anaemia are treated with oral iron which results in improved clinical outcomes. The use of intravenous iron in CCHD patients is not well studied. Purpose We aimed to compare effectiveness of intravenous iron with usual care (i.e., no therapy for CCHD patients with iron deficiency without anemia, and oral iron therapy for CCHD patients with iron deficiency anemia) on 6-minute walk distance(6MWD) after 3 months of treatment, improvement in arterial Haemoglobin saturation, Quality of life, WHO functional class and safety of intravenous Iron. Methods We enrolled 27 patients of which 13 were randomized to IV iron arm and 14 to usual treatment arm. The mean age (±SD) of enrolled patient was 23.3 (±5.55) years. 24 out of 27 patients (88.9%) were Eisenmenger Syndrome patients, while the other three patients were TOF with pulmonary atresia, DORV with pulmonary atresia and post-Fontan. 6MWD was performed to access functional capacity and WHOQOL-BREF questionnaire was used for assessment of quality of life. All the clinical findings, data and test recordings were repeated after three months. Results The mean (±SD) haemoglobin(Hb) of patients included in the study was 16.7 (±2.0) g/dl. The Hb levels improved by 0.91 (±0.85) g/dl in patients who received any form of iron therapy (IV or oral iron). Hb improvement was not significantly different between those who received IV or oral iron [IV iron: 1.15 (±0.88) g/dl, Oral iron: 0.59 (±0.79) g/dl; p= 0.12]. The baseline 6MWD was not different in both the arms (p= 0.639). The mean (±SD) 6MW distance covered in IV iron arm and usual treatment arm was 401 (±35.2) m and 408.6 (±46.5) m respectively at baseline, which improved to 425 (±28.7) m and 421.5 (±43.2) m respectively at 3 months follow up. The change in 6MWD in IV iron arm and usual treatment arm was 24 (±22.3) m and 13.1 (±16.4) m respectively. The difference of change in 6MWD between the two arms was non-significant (p= 0.157). There was a significant improvement in WHOQOL-BREF Score Domains 2,3 and 4 and there was a trend towards improvement on Domain 1 score in IV iron arm compared to usual treatment arm. WHO functional class was similar at baseline in both arms (p= 0.534). The change in WHO functional class at follow up was similar in both arms (p= 0.082) Conclusion This study demonstrated no improvement in clinical outcomes of 6MW distance, arterial hemoglobin saturation and WHO functional class. However, there was significant improvement in quality of life and iv iron was found safe and equally efficacious as oral iron for correcting iron deficiency. Further studies for determining ideal hemoglobin levels and dose of iron in CCHD patients are pertinent.