Physiological Drivers Research Articles

Unveiling the molecular and cellular links between obstructive sleep apnea-hypopnea syndrome and vascular aging.

Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.

Internal physiological drivers of leaf development in trees: Understanding the relationship between non‐structural carbohydrates and leaf phenology

Abstract Plant phenology is crucial for understanding plant growth and climate feedback. It affects canopy structure, surface albedo, and carbon and water fluxes. While the influence of environmental factors on phenology is well‐documented, the role of plant intrinsic factors, particularly internal physiological processes and their interaction with external conditions, has received less attention. Non‐structural carbohydrates (NSC), which include sugars and starch essential for growth, metabolism and osmotic regulation, serve as indicators of carbon availability in plants. NSC levels reflect the carbon balance between photosynthesis (source activity) and the demands of growth and respiration (sink activity), making them key physiological traits that potentially influence phenology during critical periods such as spring leaf‐out and autumn leaf senescence. However, the connections between NSC concentrations in various organs and phenological events are poorly understood. This review synthesizes current research on the relationship between leaf phenology and NSC dynamics. We qualitatively delineate seasonal NSC variations in deciduous and evergreen trees and propose testable hypotheses about how NSC may interact with phenological stages such as bud break and leaf senescence. We also discuss how seasonal variations in NSC levels, align with existing conceptual models of carbon allocation. Accurate characterization and simulation of NSC dynamics are crucial and should be incorporated into carbon allocation models. By comparing and reviewing the development of carbon allocation models, we highlight the shortcomings in current methodologies and recommend directions to address these gaps in future research. Understanding the relationship between NSC, source–sink relationships, and leaf phenology poses challenges due to the difficulty of characterizing NSC dynamics with high temporal resolution. We advocate for a multi‐scale approach that combines various methods, which include deepening our mechanistic understanding through manipulative experiments, integrating carbon sink and source data from multiple observational networks with carbon allocation models to better characterize the NSC dynamics, and quantifying the spatial pattern and temporal trends of the NSC‐phenology relationship using remote sensing and modelling. This will enhance our comprehension of how NSC dynamics impact leaf phenology across different scales and environments. Read the free Plain Language Summary for this article on the Journal blog.

Infanticide is driven by unfamiliarity with offspring location and associated with androgenic shifts in mimic poison frogs

Infanticide is widespread across the animal kingdom, but the physiological drivers of infanticide versus care or neglect are relatively unexplored. Here, we identified salient environmental and physiological antecedents of infanticide in the mimic poison frog (Ranitomeya imitator), a biparental amphibian. We explored potential environmental cues influencing infant-directed behavior by evaluating changes in the frequency of food provisioning and tadpole mortality after either cross-fostering tadpoles between family units or displacing tadpoles within the terraria of their parents. We found that changes in offspring location reduce care and increase infanticide. Specifically, parents fed their displaced offspring less and, in some instances, tadpole mortality increased. We also investigated whether care and infanticide were related to changes in steroid hormone concentrations in an unfamiliar setting. Infanticide of fertilized eggs and hatchlings in the new territory included cannibalism and was associated with lower testosterone concentrations, but not with changes in corticosterone. Overall, our results support earlier findings that familiarity with offspring location drives parental investment in poison frogs, while indicating an association between low androgen levels and infanticidal behavior in an amphibian.

Root traits of soybeans exposed to polyethylene films, polypropylene fragments, and biosolids

Biosolid use imports microplastics into the rhizosphere where they may interfere with root-soil-microbial interactions and cause morphological adaptations in crop root systems. Few studies have examined the response of crop roots to microplastics at documented soil concentrations, and many studies collect root traits using destructive techniques. Hence, there is little information on when and how microplastics effect the physical structure of root systems. Using the rhizobox method, soybeans (Glycine max) were grown in soil amended with biosolid microplastic mimics (polyethylene film or polypropylene fragments at 2,000 and 15,000 particles/kg dry soil) or biosolids and imaged weekly until maturity (11 weeks) using a custom scanner system. Plant biomass increased in the polyethylene treatments and decreased in the high concentration polypropylene treatment. Relative to the Control, polyethylene treatments had larger root length, reduced root diameters, reached maturity faster, had deeper root systems, and had a greater number of lateral roots. In contrast, polypropylene treatments had a mixed response, with high concentrations eliciting a lower root length, fewer laterals, and a more vertical root orientation. Segmented linear regression revealed that root growth in the Control and Biosolid treatments continued through the course of the experiment, while the microplastic treatments reached maturity up to two weeks earlier. Imagery revealed that microplastics elicited deeper rooting depth within the first week and differences in all root traits were evident by the development of the first trifoliate leaflets. Microplastic effects on root traits at early life stages suggest soil physiological drivers, while increased branching frequency and lower lateral elongation are suggestive of changes in soil nitrogen availability. The minimal difference in root traits in the biosolid treatment may be attributable to differences in microplastic properties or counteractive effects by other biosolid constituents.

Abstract P307: A Review Of The Burden, Management And Outcomes Of Patients With Aldosterone Dysregulation

Introduction: Aldosterone dysregulation (excess aldosterone production) is a complex physiological driver of uncontrolled hypertension as well as cardiovascular (CV) and kidney outcomes. Understanding the clinical and economic burden of excess aldosterone in routine practice is critical to optimizing treatment and improving long-term outcomes. This review examines the burden of excess aldosterone production as a driver of disease and its impact on clinical and economic outcomes. Hypothesis: Excess aldosterone production has a broad impact on long-term outcomes, and left untreated, contributes to worsened patient outcomes. Methods: A targeted literature review was conducted to identify articles on the burden, management and outcomes of patients with excess aldosterone production (2013 – 2024) with 27 manuscripts included. Results: More studies document the impact of excess aldosterone on organ function in the cardiovascular system and kidney (10, 8 manuscripts) compared to liver (1 manuscript). Excess aldosterone levels and aldosterone-induced oxidative stress and inflammation are associated with increased risk of CV events including myocardial infarction, heart failure, stroke, and increased morbidity and mortality. For example, Framingham Offspring Study showed increased CV disease risk with each rise in serum aldosterone levels (HR, 1.11; 95% CI, 1.02–1.21). Kidney, hepatic and metabolic manifestations are also well-documented, with implications for progression to chronic kidney disease, liver disease and metabolic syndrome. Another study reported an 11% increased risk of CKD progression associated with each doubling of serum aldosterone. Current pharmacological interventions for hypertension, including mineralocorticoid receptor antagonists, were not reported to restore normal aldosterone levels. No literature was found on the economic burden of excess aldosterone or the association between excess aldosterone production and clinical outcomes independent of blood pressure control. Conclusions: Currently available literature emphasizes the broad impact of excess aldosterone production on CV, kidney, hepatic, and metabolic outcomes. The impact on outcomes indicates that excess aldosterone production is underappreciated, with prognostic implications beyond primary aldosteronism. Current hypertension treatments do not address excess aldosterone production. These findings underscore the unmet need for novel management strategies that target excess aldosterone production.

Early-life glucocorticoids accelerate lymphocyte count senescence in roe deer

Immunosenescence corresponds to the progressive decline of immune functions with increasing age. Although it is critical to understand what modulates such a decline, the ecological and physiological drivers of immunosenescence remain poorly understood in the wild. Among them, the level of glucocorticoids (GCs) during early life are good candidates to modulate immunosenescence patterns because these hormones can have long-term consequences on individual physiology. Indeed, GCs act as regulators of energy allocation to ensure allostasis, are part of the stress response triggered by unpredictable events and have immunosuppressive effects when chronically elevated. We used longitudinal data collected over two decades in two populations of roe deer (Capreolus capreolus) to test whether higher baseline GC levels measured within the first year of life were associated with a more pronounced immunosenescence and parasite susceptibility. We first assessed immunosenescence trajectories in these populations facing contrasting environmental conditions. Then, we found that juvenile GC levels can modulate lymphocyte trajectory. Lymphocyte depletion was accelerated late in life when GCs were elevated early in life. Although the exact mechanism remains to be elucidated, it could involve a role of GCs on thymic characteristics. In addition, elevated GC levels in juveniles were associated with a higher abundance of lung parasites during adulthood for individuals born during bad years, suggesting short-term negative effects of GCs on juvenile immunity, having in turn long-lasting consequences on adult parasite load, depending on juvenile environmental conditions. These findings offer promising research directions in assessing the carry-over consequences of GCs on life-history traits in the wild.

Green Infrastructure Microbial Community Response to Simulated Pulse Precipitation Events in the Semi-Arid Western United States

Processes driving nutrient retention in stormwater green infrastructure (SGI) are not well quantified in water-limited biomes. We examined the role of plant diversity and physiochemistry as drivers of microbial community physiology and soil N dynamics post precipitation pulses in a semi-arid region experiencing drought. We conducted our study in bioswales receiving experimental water additions and a montane meadow intercepting natural rainfall. Pulses of water generally elevated soil moisture and pH, stimulated ecoenzyme activity (EEA), and increased the concentration of organic matter, proteins, and N pools in both bioswale and meadow soils. Microbial community growth was static, and N assimilation into biomass was limited across pulse events. Unvegetated plots had greater soil moisture than vegetated plots at the bioswale site, yet we detected no clear effect of plant diversity on microbial C:N ratios, EEAs, organic matter content, and N pools. Differences in soil N concentrations in bioswales and the meadow were most directly correlated to changes in organic matter content mediated by ecoenzyme expression and the balance of C, N, and P resources available to microbial communities. Our results add to growing evidence that SGI ecological function is largely comparable to neighboring natural vegetated systems, particularly when soil media and water availability are similar.

Sustained increases in atmospheric oxygen and marine productivity in the Neoproterozoic and Palaeozoic eras

A geologically rapid Neoproterozoic oxygenation event is commonly linked to the appearance of marine animal groups in the fossil record. However, there is still debate about what evidence from the sedimentary geochemical record—if any—provides strong support for a persistent shift in surface oxygen immediately preceding the rise of animals. We present statistical learning analyses of a large dataset of geochemical data and associated geological context from the Neoproterozoic and Palaeozoic sedimentary record and then use Earth system modelling to link trends in redox-sensitive trace metal and organic carbon concentrations to the oxygenation of Earth’s oceans and atmosphere. We do not find evidence for the wholesale oxygenation of Earth’s oceans in the late Neoproterozoic era. We do, however, reconstruct a moderate long-term increase in atmospheric oxygen and marine productivity. These changes to the Earth system would have increased dissolved oxygen and food supply in shallow-water habitats during the broad interval of geologic time in which the major animal groups first radiated. This approach provides some of the most direct evidence for potential physiological drivers of the Cambrian radiation, while highlighting the importance of later Palaeozoic oxygenation in the evolution of the modern Earth system.

Can biochemical tracers reveal ontogenetic trophic shift and individual prey selection in white sharks from Guadalupe Island, Northeast Pacific?

Refining the role of apex predators in marine food webs is a necessary step in predicting the consequences of their global decline under the footprint of fishing activities. White sharks (Carcharodon carcharias) are vulnerable predators, performing large migrations and able to forage on a variety of prey in different habitats. In the Northeast Pacific, juvenile and adult white sharks are found seasonally at the same aggregation sites, such as Guadalupe Island off Mexico. While adults are thought to target local pinniped colonies, very few predator-prey interactions have been documented and the diet of juveniles in this area remains poorly understood. Here we used carbon/nitrogen stable isotopes and fatty acids to characterize the trophic ecology of white sharks at Guadalupe Island. In contrast to the ontogenetic trophic shift paradigm, we detected no influence of size on muscle stable isotope and fatty acid composition, revealing no significant dietary variation between juvenile and adult sharks. Stable isotopes did not allow definitive conclusions to be drawn regarding the diet of white sharks at Guadalupe Island, due to significant variability in the contribution of different potential prey depending on the trophic discrimination factors used. However, most sharks were rich in polyunsaturated fatty acids (such as long-chain omega 3), suggesting a local diet of mainly pelagic prey (potentially large fish or cephalopods). A few individuals appeared to show recent consumption of pinnipeds, with higher proportions of saturated and monounsaturated fatty acids. These individual differences in fatty acid composition could reflect an ecological trade-off between consumption of prey rich in fat (marine mammals) versus prey rich in polyunsaturated fatty acids (pelagic prey), respectively meeting the energetic and physiological needs of white sharks. Although ontogenetic trophic changes were not able to be discerned, our results provide new insights into the physiological drivers of predator-prey interactions, which can benefit the definition of conservation strategies in a changing ocean.

Age-specific sex-differences in cerebral blood flow velocity in relation to haemoglobin levels.

Cerebral blood flow (CBF) declines with age and abnormalities in CBF are associated with age-related cerebrovascular disease and neurodegeneration. Women have higher CBF than men, although this sex-difference diminishes to some extent with age in healthy subjects. The physiological drivers of these age/sex differences are uncertain, but might be secondary to age and sex-differences in haemoglobin (Hb) level. Hb levels are inversely correlated with CBF, are lower in women, and decline with age in men, but the interrelations between these factors have not been explored systematically either in healthy subjects or across the full age-range in patients with vascular risk factors. We aimed to determine the age-specific interrelations between sex, Hb, and CBF velocity in a large cohort of patients with cerebrovascular disease. In patients with a recent transient ischaemic attack or minor stroke (Oxford Vascular Study) and no ipsilateral or contralateral stenosis of the carotid or intracranial arteries, we related peak-systolic velocity (PSV) and other parameters on transcranial Doppler ultrasound (TCD) of the middle cerebral artery to sex, age, Hb and vascular risk factors. Of 958 eligible subjects (mean age/SD = 68.04/14.26, 53.2% male), younger women (age < 55 years) had higher CBF velocities than men (mean sex difference in PSV at age < 55 years = 16.31 cm/s; p < 0.001), but this difference declined with age (interaction p < 0.001), such that it was no longer significant at age 75-84 (∆PSV = 3.26 cm/s; p = 0.12) and was reversed at age ⩾ 85 (∆PSV = -7.42 cm/s; p = 0.05). These changes mirrored trends in levels of Hb, which were higher in men at age < 55 (∆Hb = 1.92 g/dL; p < 0.001), but steadily decreased with age in men but not in women (interaction p < 0.001), with no residual sex-difference at age ⩾ 85 (∆Hb = 0.12 g/dL; p = 0.70). There was an inverse correlation between Hb and PSV in both women and men (both p ⩽ 0.01), and the sex-difference in PSV at age < 55 was substantially diminished after adjustment for Hb (∆PSV = 6.92; p = 0.036; ∆PSV = 5.92, p = 0.13 with further adjustment for end-tidal CO2). In contrast, the sex difference in PSV was unaffected by adjustment for systolic and diastolic blood pressure, heart rate, and vascular risk factors (history of hypertension, diabetes, hyperlipidaemia and smoking). CBF velocity is strongly correlated with Hb level at all ages, and sex-differences in CBF velocity appear to be explained in major part by age-related sex-differences in Hb.

Aerobic methane production in Scots pine shoots is independent of drought or photosynthesis.

Shoot-level emissions of aerobically produced methane (CH4) may be an overlooked source of tree-derived CH4, but insufficient understanding of the interactions between their environmental and physiological drivers still prevents the reliable upscaling of canopy CH4 fluxes. We utilised a novel automated chamber system to continuously measure CH4 fluxes from the shoots of Pinus sylvestris (Scots pine) saplings under drought to investigate how canopy CH4 fluxes respond to the drought-induced alterations in their physiological processes and to isolate the shoot-level production of CH4 from soil-derived transport and photosynthesis. We found that aerobic CH4 emissions are not affected by the drought-induced stress, changes in physiological processes, or decrease in photosynthesis. Instead, these emissions vary on short temporal scales with environmental drivers such as temperature, suggesting that they result from abiotic degradation of plant compounds. Our study shows that aerobic CH4 emissions from foliage are distinct from photosynthesis-related processes. Thus, instead of photosynthesis rates, it is more reliable to construct regional and global estimates for the aerobic CH4 emission based on regional differences in foliage biomass and climate, also accounting for short-term variations of weather variables such as air temperature and solar radiation.

Explainable machine learning for predicting stomatal conductance across multiple plant functional types

Stomatal conductance (gs) is a key leaf-level function controlling water, carbon, and energy exchange between vegetation and the surrounding environment. Conventionally, semi-empirical models have been used to model gs, but these models require re-parameterization as ecosystems undergo phenological changes over the growing season. In contrast, machine learning (ML) models offer a potential path to overcome this problem but are less interpretable than process-based models. This study explores ML as an approach to develop flexible and robust models of gs for a range of plant functional types (PFTs), including C3 crops, C3 grasses, shrubs, and tree species across different continents. An explainable machine-learning approach (eXML) was used here to provide novel interpretations and insights into the ML model formulations and relative predictor importance. We contrast the performance of three ML architectures: extreme gradient boosting, random forests, and neural networks. Models were developed and examined using many combinations of environmental and physiological predictors. The results demonstrated that ML models significantly outperform conventional semi-empirical models in predicting gs responses to the environment, while not requiring re-parameterization as is required in the semi-empirical paradigm. Particular focus is placed on models formulated around predictor sets that are: (a) relevant to gs estimation in modern terrestrial biophysical simulation models, and (b) composed of variables describing environmental and physiological drivers that can be remotely sensed non-invasively. “Generalized” models developed using data from all four PFTs demonstrated strong predictive performance using only three predictor variables, capturing 63–80 % of the variability in stomatal conductance across all ML architectures. Four predictor variables resulted in models capturing 79–83 % of gs variability, and models developed using all five predictor variables examined here were able to capture as much as 87 % of gs variability across all PFTs. Uncertainty in gs predictions was quantified using quantile regression. Shapley additive explanations was applied to unravel instance-based positive and negative contributions of environmental and physiological predictors to gs modeling, while illustrating that the models are consistent with the underlying ecophysiology. This work demonstrates the power of ML to introduce a new paradigm in the simulation of highly dynamic ecophysiological processes critical to environmental prediction.

Measured leaf dark respiratory CO2 -release is not controlled by stomatal conductance.

Leaf dark respiratory CO2 -release (RD ) is, according to some literature, dependent on the rate of leaf transpiration. If this is true, then at a given vapor pressure deficit, the leaf stomatal conductance (gs ) will be expected to be a controlling factor of measured RD at any given time. We artificially lowered leaf gs by applying abscisic acid (ABA). Although leaf RD generally covaried temporally with gs , artificially lowering gs by applying ABA does not affect the measured leaf RD . These results indicate that observed diel fluctuations in gs are not directly influencing the measured leaf RD , thereby simplifying both future studies and the interpretation of past studies of the underlying environmental- and physiological drivers of temporal variation in leaf RD .

Sex differences in heart rate variability measures that predict alcohol drinking in rats.

Problem alcohol drinking continues to be a substantial cost and burden. In addition, alcohol consumption in women has increased in recent decades, and women can have greater alcohol problems and comorbidities. Thus, there is a significant need for novel therapeutics to enhance sex-specific, individualized treatment. Heart rate (HR) and HR variability (HRV) are of broad interest because they may be both biomarkers for and drivers of pathological states. HRV reflects the dynamic balance between sympathetic (SNS, 'fight or flight') and parasympathetic (PNS, 'rest and digest') systems. Evidence from human studies suggest PNS predominance in women and SNS in men during autonomic regulation, indicating the possibility of sex differences in risk factors and physiological drivers of problem drinking. To better understand the association between HRV sex differences and alcohol drinking, we examined whether alcohol consumption levels correlated with time domain HRV measures (SDNN and rMSSD) at baseline, at alcohol drinking onset, and across 10min of drinking, in adult female and male Wistar rats. In particular, we compared both HRV and HR measures under alcohol-only and compulsion-like conditions (alcohol + 10mg/L quinine), because compulsion can often be a significant barrier to treatment of alcohol misuse. Importantly, previous work supports the possibility that different HRV measures could be interpreted to reflect PNS versus SNS influences. Here, we show that females with higher putative PNS indicators at baseline and at drinking onset had greater alcohol consumption. In contrast, male intake levels related to increased potential SNS measures at drinking onset. Once alcohol was consumed, HR predicted intake level in females, perhaps a pharmacological effect of alcohol. However, HRV changes were greater during compulsion-like intake versus alcohol-only, suggesting HRV changes (reduced SNS in females, reduced PNS and increased HR in males) specifically related to aversion-resistant intake. We find novel and likely clinically relevant autonomic differences associated with biological sex and alcohol drinking, suggesting that different autonomic mechanisms may promote differing aspects of female and male alcohol consumption.

In situ seasonal patterns of root auxin concentrations and meristem length in an arctic sedge.

Seasonal dynamics of root growth play an important role in large-scale ecosystem processes; they are largely governed by growth regulatory compounds and influenced by environmental conditions. Yet, our knowledge about physiological drivers of root growth is mostly limited to laboratory-based studies on model plant species. We sampled root tips of Eriophorum vaginatum and analyzed their auxin concentrations and meristem lengths biweekly over a growing season in situ in a subarctic peatland, both in surface soil and at the permafrost thawfront. Auxin concentrations were almost five times higher in surface than in thawfront soils and increased over the season, especially at the thawfront. Surprisingly, meristem length showed an opposite pattern and was almost double in thawfront compared with surface soils. Meristem length increased from peak to late season in the surface soils but decreased at the thawfront. Our study of in situ seasonal dynamics in root physiological parameters illustrates the potential for physiological methods to be applied in ecological studies and emphasizes the importance of in situ measurements. The strong effect of root location and the unexpected opposite patterns of meristem length and auxin concentrations likely show that auxin actively governs root growth to ensure a high potential for nutrient uptake at the thawfront.

Thermal optima in the hypoxia tolerance of marine ectotherms: Physiological causes and biogeographic consequences.

The minimum O2 needed to fuel the demand of aquatic animals is commonly observed to increase with temperature, driven by accelerating metabolism. However, recent measurements of critical O2 thresholds ("Pcrit") reveal more complex patterns, including those with a minimum at an intermediate thermal "optimum". To discern the prevalence, physiological drivers, and biogeographic manifestations of such curves, we analyze new experimental and biogeographic data using a general dynamic model of aquatic water breathers. The model simulates the transfer of oxygen from ambient water through a boundary layer and into animal tissues driven by temperature-dependent rates of metabolism, diffusive gas exchange, and ventilatory and circulatory systems with O2-protein binding. We find that a thermal optimum in Pcrit can arise even when all physiological rates increase steadily with temperature. This occurs when O2 supply at low temperatures is limited by a process that is more temperature sensitive than metabolism, but becomes limited by a less sensitive process at warmer temperatures. Analysis of published species respiratory traits suggests that this scenario is not uncommon in marine biota, with ventilation and circulation limiting supply under cold conditions and diffusion limiting supply at high temperatures. Using occurrence data, we show that species with these physiological traits inhabit lowest O2 waters near the optimal temperature for hypoxia tolerance and are restricted to higher O2 at temperatures above and below this optimum. Our results imply that hypoxia tolerance can decline under both cold and warm conditions and thus may influence both poleward and equatorward species range limits.

Predictors of sustained physical activity: behaviour, bodily health, and the living environment.

This study examined the determinants of sustained physical activity. Eighty-four participants undertook a 7-weeks walking regime (i.e., a 1-h biometrically-monitored walk, at least 5days/week), with bioelectrical impedance (BIA) and total cholesterol capillary blood measurements performed before and after programme. To investigate behavioural habit formation, 7weeks after walking termination, all participants were interviewed and (health) re-tested. Data were modelled with an artificial neural network (ANN) cascading algorithm. Our results highlight the successful prediction of continued physical activity by considering one's physical fitness state, the environmental living context, and risk for cardiovascular disease. Importantly, those artificial neural network models also taking body mass index (BMI) and blood cholesterol as predictors excel at predicting walking continuation (i.e., predictions with 93% predictability). These results are first to highlight the type and importance of available physiological drivers in maintaining a sustained physical activity regime such as walking. They are discussed within the framework of habit formation and the nowadays health and/or wellbeing focus.

Faculty Training on Navigating Gender and Sex in Medical Education.

Language that assumes gender and sex are binary and aligned is pervasive in medicine and is often used when teaching on physiology and pathology. Information presented through this lens oversimplifies disease mechanisms and poorly addresses the health of gender and sexually diverse (GSD) individuals. We developed a training session to help faculty reference gender and sex in a manner that would be accurate and inclusive of GSD health. The 1-hour session for undergraduate and graduate medical educators highlighted cisgender and binary biases in medical teachings and introduced a getting-to-the-root mindset that prioritized teaching the processes underlying differences in disease profiles among gender and sex subpopulations. The training consisted of 30 minutes of didactic teaching and 20 minutes of small-group discussion. Medical education faculty attended and self-reported knowledge and awareness before and after the training. Results were compared using paired t tests. Expenses included fees for consultation and catering. Forty faculty participated (pretraining survey n = 36, posttraining survey n = 21). After the training, there was a significant increase in self-reported awareness of the difference between gender and sex (p = .002), perceived relevance of gender to teachings (p = .04), and readiness to discuss physiological drivers of sex-linked disease (p = .005). Participants reported increased understanding and consideration of gender and sex in medical education; feedback emphasized a desire for continued guidance. This easily adaptable session can provide an introduction to a series of medical teachings on gender and sex.

Circadian distribution of epileptiform discharges in epilepsy: Candidate mechanisms of variability.

Epilepsy is a serious neurological disorder characterised by a tendency to have recurrent, spontaneous, seizures. Classically, seizures are assumed to occur at random. However, recent research has uncovered underlying rhythms both in seizures and in key signatures of epilepsy-so-called interictal epileptiform activity-with timescales that vary from hours and days through to months. Understanding the physiological mechanisms that determine these rhythmic patterns of epileptiform discharges remains an open question. Many people with epilepsy identify precipitants of their seizures, the most common of which include stress, sleep deprivation and fatigue. To quantify the impact of these physiological factors, we analysed 24-hour EEG recordings from a cohort of 107 people with idiopathic generalized epilepsy. We found two subgroups with distinct distributions of epileptiform discharges: one with highest incidence during sleep and the other during day-time. We interrogated these data using a mathematical model that describes the transitions between background and epileptiform activity in large-scale brain networks. This model was extended to include a time-dependent forcing term, where the excitability of nodes within the network could be modulated by other factors. We calibrated this forcing term using independently-collected human cortisol (the primary stress-responsive hormone characterised by circadian and ultradian patterns of secretion) data and sleep-staged EEG from healthy human participants. We found that either the dynamics of cortisol or sleep stage transition, or a combination of both, could explain most of the observed distributions of epileptiform discharges. Our findings provide conceptual evidence for the existence of underlying physiological drivers of rhythms of epileptiform discharges. These findings should motivate future research to explore these mechanisms in carefully designed experiments using animal models or people with epilepsy.

Dissecting the complexity of pediatric blood transfusions and risk of adverse reactions in Aotearoa New Zealand.

Children have different clinical and physiological drivers for transfusion from adult recipients. However, adverse transfusion reactions (ATRs) in pediatric patients are usually reported using the same criteria as for adults. Broad assessments of pediatric ATRs neglect substantial variation in different developmental stages. This retrospective study included 342,950 patients, ~2.43 million transfusions, and 5,540 ATR reports collated from New Zealand hospitals between 2005 and 2021. Using 16 years as the upper age limit, 138,856 pediatric transfusions and 402 pediatric ATR reports were identified and dissected at three levels: pediatric as a whole, pediatric developmental stage (i.e., neonate, infant, preschool, and school), and chronological age to identify patients at high risk of ATRs. Multivariate logistic regression analysis was followed to quantify risk factors. Pediatric recipients had a higher ATR risk than adults (p=6.9-07) but the high risk was associated mainly with children older than 2 years. Neonates and infants accounted for 75.0% of pediatric recipients but had much lower ATR rates than adults. Pediatric transfusion recipients showed a clear male bias prior to age 11 years and then a female bias. However, gender difference in experiencing ATRs was significant only after age 13 years (p=2.3-04). Analyses focusing on the high-risk group revealed allergic reactions being the cause of the elevated risk and identified the main risk factors of number of transfusions (p=4.5-10) and multiple types of components transfused (p=2.0-13). The identified ATR risk factors signal linkage with the biological drivers for transfusion. Low ATR rates in infancy could also be attributed to use of neonatal components, low transfusions per patient, and less developed immunity. The relative increase in female recipients from age 11 may be associated with increased red blood cell demand following puberty.