Joyner, Michael J.

Abstract Hypoxia constrains cerebral oxygen availability and challenges brain function and stability. Although hypoxia-responsive functional connectivity (HR-FC) reorganizes rapidly with declining arterial oxygen partial pressure, its relationship to local neurovascular activity remains unclear. We examined time-resolved amplitude of low-frequency fluctuations (ALFF) in blood-oxygenation-level dependent (BOLD) fMRI during graded acute hypoxia in healthy adults, performing a continuous cognitive test (Go/No-go task) with concurrent physiological monitoring. Dynamic ALFF and functional connectivity were estimated using a sliding-window approach and analyzed across large-scale brain networks defined by Schaefer’s 17-network parcellation. Severe hypoxia elicited temporally dissociated responses across modalities. Functional connectivity increased monotonically, whereas ALFF exhibited pronounced nonlinear modulation, including phase-dependent divergence across networks. During hypoxic decompensation, the default mode network (DefaultA) showed marked ALFF suppression, whereas a ventral secondary somatosensory-dominant network (SomMotB) exhibited preferential preservation despite similar engagement in HR-FC. Together, these findings indicate that network-level ALFF captures a distinct yet complementary layer of functional dynamics, with a temporal profile distinct from functional connectivity. Spontaneous BOLD dynamics during acute hypoxia reflect structured network-level modulation rather than a uniform suppression attributable solely to reduced oxygen availability. These findings support a conceptual framework of cerebral oxygen budgeting , in which metabolic constraints reshape functional dynamics across brain networks.

This study investigated the first multiomics data for association with tolerance to central hypovolemia in humans. Analyzing gene expression, proteins, and genetic variants in individuals with high and low tolerance to simulated hemorrhage, the findings show that severe blood loss causes widespread transcriptional changes, including the activation of innate immune system pathways and inhibition of gas transport processes. This research can help identify molecular factors that influence individuals’ tolerance levels for progressive blood loss.

OBJECTIVES: Vasoplegia is a common complication of cardiac surgery that uses cardiopulmonary bypass and contributes to morbidity and mortality, yet a consensus definition does not exist. The objective of this study was to evaluate the diagnostic criteria and definitions used to characterize vasoplegia and how different criteria influence incidence estimates. DATA SOURCES: Ovid Embase, Ovid MEDLINE, Scopus, Web of Science Core Collection, ClinicalTrials.gov, Ovid Cochrane Central Register of Controlled Trials, and the World Health Organization’s International Clinical Trials Registry Platform clinical trials registry. STUDY SELECTION: Randomized clinical trials and observational studies reporting on vasoplegia in adults undergoing any type of cardiac surgery that used cardiopulmonary bypass. DATA EXTRACTION: Proportional meta-analysis using a random-effects model and the inverse variance method was used to calculate the pooled incidence of vasoplegia and its clinical outcomes. DATA SYNTHESIS: A total of 68 studies encompassing 56,580 patients were identified, from which 63 unique vasoplegia definitions were used. Blood pressure ( n = 57 studies, 84%) and cardiac output ( n = 50 studies, 74%) were among the most common criteria used in vasoplegia definitions; however, there was a vast variety of threshold values applied within these criteria and all other criteria comprising the definitions. The pooled incidence of vasoplegia was 21% (95% CI, 17–25%), acute kidney injury was 32% (95% CI, 21–45%), and mortality was 12% (95% CI, 9–16%). Subgroup analysis revealed that transplantation and left ventricular assist device implantation surgeries, and those with baseline left ventricular ejection fraction less than 40% had a significantly greater incidence of vasoplegia. CONCLUSIONS: The published literature varies greatly in the criteria used to define vasoplegia associated with on-pump cardiac surgery. Generation and adoption of a unified definition for vasoplegia must be an international priority.

This study leverages an experiment of nature framework to examine sex-based differences in ultraendurance swimming using English Channel performance data. Males were faster than females, with the greatest differences observed among older swimmers and top performers. Performance was optimal in moderately cool water temperatures (17–18°C). These findings highlight how naturally occurring endurance events provide unique opportunities to study physiological limits and the combined influences of sex, age, and environment on human performance.

SUMMARY COVID-19 convalescent plasma (CCP) was the first specific therapy deployed for treating SARS-CoV-2 infection. CCP was successfully deployed in both resource-poor and resource-rich countries, establishing that convalescent plasma (CP) is a feasible option for combating the next pandemic. CCP reduced mortality and progression to hospitalization when used early in the disease with high-titer units. This knowledge was gained from a worldwide effort that included more than 50 countries. However, the deployment of CCP was haphazard and varied among countries. Clinical studies suffered from a lack of standardization regarding study design, CCP antibody dosing, timing of administration, and participant disease severity. Unfortunately, the hard-won knowledge from the serum therapy era in the early 20th century, which indicated that effective antibody therapy requires early use in the disease with a sufficient antibody dose, was largely forgotten. Many studies tested CCP late in the disease or without sufficient antibody titer and thus reported negative findings. Trial heterogeneity made it difficult to combine the results of studies. However, despite tremendous heterogeneity in study design and participant populations, meta-analysis revealed strong signals of efficacy when given early with high antiviral-specific antibody levels. When the next pandemic occurs, humanity is likely to resort to CP again. To avoid another chaotic rollout, planning for CP use should begin well before that emergency arrives and must involve both physician education on the principles of antibody therapy and clinical trial designs that test its efficacy in optimal conditions, which include early use with sufficient antibody doses.

AbstractInterstitial lung disease (ILD) encompasses pulmonary disorders characterized by chronic inflammation and fibrosis that disrupt pulmonary gas exchange. While ILD‐related changes in the lung parenchyma are well‐documented, less is known about how ILD affects luminal area within the large conducting airways. This retrospective, case–control study tested the hypothesis that patients with ILD would have greater large conducting airway luminal areas than healthy matched controls. Three‐dimensional reconstructions of computed tomography images were used to quantify airway luminal areas in patients with ILD (n = 82; 54% female) and healthy controls matched for age, sex, and height. Patients with ILD had 16%–22% greater airway luminal areas across all seven measured large conducting airways compared to controls (all p < 0.001). Among patients with ILD, males had 17%–34% greater height‐normalized airway luminal areas than females (all p < 0.05). These data provide evidence that ILD is associated with greater large conducting airway luminal area, even when matched for key demographic factors. Consistent with observations in health, males with ILD exhibited greater height‐normalized airway size than females. These findings offer new insight into airway remodeling in ILD and highlight potential sex differences in airway luminal area.

AbstractFatiguing inspiratory work has been shown to evoke a sympathetically mediated reflex that has systemic cardiovascular consequences, including increases in heart rate and blood pressure and a decrease in resting limb vascular conductance. Moreover, the response to this reflex appears to be attenuated in females compared with males. It remains to be seen whether this respiratory muscle metaboreflex also exerts an effect on cerebral blood flow. Cerebral blood flow is tightly regulated to maintain homeostasis and critical function. Therefore, it stands to reason that cerebrovascular haemodynamics would not be compromised through this respiratory muscle metaboreflex. We hypothesized that fatiguing inspiratory work would reduce resting limb conductance, but cerebral blood flow would be minimally impaired. Females (34 ± 10 years old, n = 12) and males (31 ± 8 years old, n = 12) performed a 5 min, high‐intensity bout of inspiratory pressure threshold loading (IPTL) designed to evoke the respiratory muscle metaboreflex. In response to IPTL, mean arterial pressure increased in both males and females (p < 0.001), and limb vascular conductance decreased to a greater degree in males than in females (p = 0.005). The cerebrovascular conductance index was higher in females (p = 0.007) but not affected by IPTL (p = 0.417). Our findings suggest that cerebral blood flow is spared from the redistribution of blood flow in response to fatiguing inspiratory work and that this protection is true in both males and females.