The adrenal gland, essential for survival, contains the medulla and cortex. Chromaffin cells (ChrCs) in the adrenal medulla control the fight-or-flight response by releasing catecholamines like epinephrine and norepinephrine. Recent findings reveal that ChrCs originate from two progenitors: 20% from developmentally early, neural crest-derived sympathoadrenal progenitors (SAPs) and 80% from the later Schwann cell precursors (SCPs). We generated functional adrenomedullary organoids from human pluripotent stem cells (hPSCs) via both pathways and in mixed (20% SAP, 80% SCP-derived) cultures. When implanted into chicken embryos, the organoids migrated and integrated into the adrenal gland anlagen. In vitro , they released norepinephrine and epinephrine in response to stimulation. Single-cell transcriptomics confirmed developmental trajectories matching human fetal data and allowed the identification of a novel ChrC subtype specifically derived from the SAP that may be responsible for mediating the severe stress reaction via EPI. Assessing developmental knowledge in this human system, we found that SAPs differentiated into ChrCs, but not sympathetic neurons or Schwann cells, showing limited plasticity. Meanwhile, SCPs could produce various cell types but not sympathetic neurons. Furthermore, our work reveals that under stress conditions, SAP-derived ChrCs mainly release epinephrine, while SCP-derived ChrCs release norepinephrine, highlighting distinct functions based on developmental origin. These organoids provide valuable models for studying ChrC development, interactions, and adrenal pathologies.

Kounis syndrome is an acute coronary syndrome triggered by an allergic or anaphylactic reaction. Diagnosis can be challenging when epinephrine is administered during the same episode because both the allergic reaction and epinephrine may influence coronary vascular tone. We report the case of a 62-year-old man with no previous cardiac history who developed anaphylactic shock after a hornet sting to the upper lip. Acute constrictive chest pain began during the allergic reaction, before epinephrine administration. He was promptly treated with 0.55 mg of epinephrine, methylprednisolone, and dexchlorpheniramine. An electrocardiogram obtained during the acute episode showed ST-segment depression in leads III, aVF, and V3-V6. The chest pain and electrocardiographic abnormalities subsequently resolved. Troponin peaked at 208 ng/L. Transthoracic echocardiography showed preserved left ventricular systolic function without regional wall-motion abnormalities. Coronary angiography revealed only minor non-obstructive coronary irregularities, with no culprit lesion, and follow-up cardiac magnetic resonance imaging was normal. The overall presentation was consistent with type I Kounis syndrome, most likely caused by transient allergy-mediated coronary vasospasm. The onset of chest pain before epinephrine administration was an important element supporting the allergic coronary event as the primary mechanism.

Rice-paddy amphibians are routinely exposed to neonicotinoids, yet whether such exposure causes endocrine, mitochondrial, and neuromuscular toxicity remains poorly understood. Herein, we combined field surveillance across 39 rice-paddy sites in Zhejiang, China, with a 60-day exposure of adult Pelophylax nigromaculatus to thiamethoxam. Field monitoring in July detected all five neonicotinoids in 69.2% of rice-paddy water samples with summed thiamethoxam-equivalent concentrations ranging from 52.18 to 1282.69 μg/L, while concentrations in wild tadpoles ranged from 6.45 to 113.39 μg/kg. Laboratory thiamethoxam exposure (0.5 and 5 mg/L) resulted in predominant hepatic accumulation and detectable brain residues. Notably, thiamethoxam reduced serum T3, T4, FT3, and FT4, increased L-tyrosine, epinephrine, and dopamine, with dysregulation of HPT-axis-related genes. In skeletal muscle, thiamethoxam inhibited mitochondrial membrane potential, respiratory chain complexes I, II, III, V, as well as basal and maximal mitochondrial respiration (up to 55%). These defects coincided with fragmented AChR clusters, reduced receptor content, and impaired gastrocnemius force across 20-60 Hz in the 5 mg/L group. Some responses varied between sexes, with AChR fluorescence intensity significantly reduced only in females in 5 mg/L. Structural equation modeling supported a thyroid to mitochondrial pathway, in which thiamethoxam reduced integrated thyroid hormone status (β = -0.91), while thyroid hormone status positively predicted mitochondrial membrane potential (β = 0.79) and maximal respiration (β = 0.71). These findings identify thyroid hormone-linked mitochondrial dysfunction as a mechanistic bridge between thiamethoxam exposure and neuromuscular impairment.

Based on current data, immediate activation of EMS in all cases of anaphylaxis does not provide significant benefit. Instead, the option for home management or a "watchful-waiting" approach allowing for increased patient autonomy in anaphylaxis management and emphasizing prompt epinephrine use at home. In this model, patients are instructed to quickly administer epinephrine and monitor for resolution of symptoms. The option to escalate care is available, but in 90% of cases, symptoms will resolve after one dose of epinephrine, rendering EMS/ED involvement unnecessary. Thus, patients can immediately treat their anaphylaxis from the comfort of home while avoiding complications from delayed epinephrine use.

Neurosurgical patients commonly experience significant preoperative anxiety, which can negatively impact surgical outcomes and recovery trajectories. Music, as a powerful neurophysiological modulator of the human stress response, offers a non-pharmacological, non-invasive and cost-effective approach to anxiolysis by stabilising the hypothalamic-pituitary-adrenal axis and autonomic nervous system. The goal of this study is to evaluate the effects of live and recorded music on preoperative stress, serum-level and plasma-level biomarkers, perceived pain, anxiety and mood states in neurosurgical cancer patients.

Cyclic blood pressure fluctuations in pheochromocytoma are extremely rare, and previously reported cases have been limited to adults. We report a 5-year-old boy with von Hippel-Lindau disease and a left adrenal pheochromocytoma who developed rapid cyclic blood pressure fluctuations immediately after tracheal intubation. Despite preoperative doxazosin (titrated from 0.5 to 3 mg/day over 27 days) and fluid loading, systolic blood pressure oscillated between 50 and 150 mmHg at approximately 7-min intervals after tracheal intubation. The fluctuations were independent of surgical manipulation and refractory to phenylephrine and phentolamine. Plasma norepinephrine was markedly elevated before tumor manipulation. After tumor resection, profound vasoplegic hypotension required high-dose norepinephrine, epinephrine, and vasopressin; hemodynamics gradually stabilized, and all vasoactive agents were discontinued on postoperative Day 3. This case demonstrates that pediatric pheochromocytoma can develop cyclic blood pressure fluctuations similar to those in adults and underscores the importance of individualized preoperative α-blockade and strict postoperative hemodynamic management after tumor resection.

Anaphylaxis is a severe, rapidly progressing, and potentially life-threatening emergency requiring prompt, evidence-based intervention. This study assessed pre-hospital emergency healthcare professionals' knowledge of anaphylaxis diagnosis, acute management, and treatment protocols in line with current clinical guidelines. A descriptive cross-sectional study was conducted between February and April 2025 among physicians, paramedics, and emergency medical technicians (EMTs) working in Emergency Medical Services (EMS) stations. Data were collected via a 21-item Google Forms survey covering demographics and key knowledge domains based on established pediatric anaphylaxis guidelines. A total of 322 professionals participated: paramedics (n = 214, 66.5%), EMTs (n = 73, 22.7%), and physicians (n = 35, 10.9%). Although most reported prior anaphylaxis training (90.0%) and clinical encounters (87.6%), only 52.2% correctly identified all three diagnostic criteria. Regarding pharmacologic management, 81.7% recognized epinephrine as first-line treatment, with physicians performing best (94.3%) compared to paramedics (81.8%) and EMTs (75.3%). Similarly, 81.1% correctly identified the intramuscular route, with physicians again demonstrating superior knowledge (95.5%). However, major deficiencies were noted in appropriate patient positioning (52.2%) and epinephrine auto-injector use (50.6%), with significant inter-professional differences across both domains. Substantial knowledge gaps exist among pre-hospital emergency providers regarding anaphylaxis diagnosis, patient positioning, and auto-injector administration. Targeted training and standardized protocols are urgently needed to enhance competency and improve patient safety in pre-hospital anaphylaxis management.

Environmental heat stress is an emerging ecological problem, yet the physiological mechanisms linking repeated heat exposure to cardiovascular disease risk remain incompletely understood. Here, we investigated the systemic, cardiovascular, metabolic, and immune consequences of intermittent environmental heat stress. C57BL/6J Mice were exposed to intermittent hyperthermia (30°C-37°C, 3 h/day, 4 days/week) for up to four weeks under controlled environmental conditions. The core body temperature, blood pressure, and endothelial activation were measured by SoHo telemetry devices, tail-cuff, and intravital microscopy, respectively. During heat exposure (> 33°C) there was a level dependent increase in core body temperature and water and food intake exposures. Exposure to 37°C elicited a robust neuroendocrine stress response characterized by a 2-4-fold increase in plasma corticosterone levels, > 50% reductions in plasma epinephrine, and a robust induction of heat shock proteins in the vasculature. Heat exposure also transiently reduced systolic and diastolic blood pressure by ~10 mmHg and > 30% depletion in circulating immune cell populations. Despite this systemic leukopenia, repeated heat stress (37°C, 3 h/day, 4 days/week, 4-weeks) increased leukocyte rolling and adhesion to the vascular endothelium (> 3-fold), indicative of enhanced endothelial activation. In contrast, repeated heat exposure had minimal effects on cardiac systolic function, arterial stiffness, plasma lipid levels, or markers of overt organ injury. These findings demonstrate that repeated environmental heat stress induces coordinated neuroendocrine, vascular, immune, and metabolic adaptations characterized by activation of heat shock pathways, immune remodeling, and endothelial activation that precede cardiovascular dysfunction.

Pneumatic tourniquets have traditionally been used to achieve a bloodless operative field in foot and ankle surgery but are associated with postoperative pain, ischemia-reperfusion injury, and neurologic complications. This review compares tourniquet-based and epinephrine-based hemostasis regarding mechanisms, safety, effectiveness, and outcomes. Tourniquets provide reliable visualization, particularly in complex or prolonged procedures, but increase pain and tissue injury. Epinephrine induces transient vasoconstriction while preserving partial perfusion, demonstrating strong safety with reduced postoperative pain and opioid use. Optimal results require proper dosing and timing. Hemostatic strategy should be individualized based on procedure and patient factors. Further studies comparing standardized protocols are needed.