Cerebral hemodynamic and systemic physiological changes in trained freedivers completing sled-assisted dives to two different depths.

While existing literature covers significant detail on the physiology of human freediving, the lack of standardized protocols has hindered comparisons due to confounding variables such as exercise and depth. By accounting for these variables, direct depth-dependent impacts on cardiovascular and blood oxygen regulation can be investigated. In this study, depth-dependent effects on 1) cerebral hemodynamic and oxygenation changes, 2) arterial oxygen saturation (SpO2), and 3) heart rate during breath-hold diving without confounding effects of exercise were investigated. Six freedivers (51.0 ± 12.6 years; mean ± s.d.), instrumented with continuous-wave near-infrared spectroscopy for monitoring cerebral hemodynamic and oxygenation measurements, heart rate and SpO2, performed sled-assisted breath-hold dives to 15 m and 42 m. Arterial blood gas tensions were validated through cross-sectional periodic blood sampling. Cerebral hemodynamic changes were characteristic of breath-hold diving, with changes during ascent from both depths likely driven by decreasing SpO2 due to lung expansion. While SpO2 was significantly lower following 42 m dives (t(5) = -4.183, p < 0.05), mean cerebral arterial-venous blood oxygen saturation remained at 74% following dives to both depths. Cerebral oxygenation during ascent from 42 m may have been maintained through increased arterial delivery. Heart rate was variable with no significant difference in minimum heart rate between both depths (t(5) = -1.017, p > 0.05). This study presents a standardized methodology, which could provide a basis for future research on human freediving physiology and uncover ways in which freedivers can reduce potential risks of the sport.

Neuromuscular impairment at different stages of human sarcopenia.

BACKGROUND: Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age-related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties. METHODS: We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants. RESULTS: Thirty-nine older individuals were non-sarcopenic (NS), 31 pre-sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross-sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P < 0.0001). Handgrip force and the Short Physical Performance Battery score also showed a diminishing trend. iEMG analyses revealed elevated near fibre segment jitter in NS, PS and S compared with Y (Y vs. NS and S: P < 0.0001; Y vs. PS: P = 0.0169), suggestive of age-related impaired NMJ transmission. Increased C-terminal agrin fragment (P < 0.0001) and altered caveolin 3 protein expression were consistent with age-related NMJ instability in all the older groups. The iMUNE was lower in all older groups (P < 0.0001), confirming age-related loss of MUs. An age-related increase in MU potential complexity was also observed. These observations were accompanied by increased muscle denervation and axonal damage, evinced by the increase in neural cell adhesion molecule-positive fibres (Y vs. NS: P < 0.0001; Y vs. S: P = 0.02) and the increase in serum concentration of neurofilament light chain (P < 0.0001), respectively. Notably, most of these MU and NMJ parameters did not differ when comparing older individuals with or without sarcopenia. CONCLUSIONS: Alterations in MU properties, axonal damage, an altered innervation profile and NMJ instability are prominent features of the ageing of the neuromuscular system. These neuromuscular alterations are accompanied by muscle wasting and weakness; however, they appear to precede clinically diagnosed sarcopenia, as they are already detectable in older NS individuals.

Consumption of Sylimarin, Pyrroloquinoline Quinone Sodium Salt and Myricetin: Effects on Alcohol Levels and Markers of Oxidative Stress-A Pilot Study.

BACKGROUND: Alcohol abuse is one of the most common causes of mortality worldwide. This study aimed to investigate the efficacy of a treatment in reducing circulating ethanol and oxidative stress biomarkers. METHODS: Twenty wine-drinking subjects were investigated in a randomized controlled, single-blind trial (ClinicalTrials.gov. Identifier: NCT06548503; Ethical Committee of the University of Padova (HEC-DSB/12-2023) to evaluate the effect of the intake of a product containing silymarin, pyrroloquinoline quinone sodium salt, and myricetin (referred to as Si.Pi.Mi. for this project) on blood alcohol, ethyl glucuronide (EtG: marker for alcohol consumption) and markers of oxidative stress levels (Reactive Oxygen Species-ROS, Total Antioxidant Capacity-TAC, CoQ10, thiols redox status, 8-isoprostane, NO metabolites, neopterin, and uric acid). The effects of the treatment versus placebo were evaluated acutely and after 1 week of supplementation in blood and/or saliva and urine samples. RESULTS: Si.Pi.Mi intake reduced circulating ethanol after 120 min (-33%). Changes in oxidative stress biomarkers, particularly a TAC (range +9-12%) increase and an 8-isoprostane (marker of lipidic peroxidation) decrease (range -22-27%), were observed too. CONCLUSION: After the administration of Si.Pi.Mi, the data seemed to suggest a better alcohol metabolism and oxidative balance in response to wine intake. Further verification is requested.

Local Anesthetic Systemic Toxicity Joint Management in the Prehospital Environment: A Case Report.

Local anesthetic systemic toxicity (LAST) is a potentially life-threatening complication that may occur after local anesthetic injection. After reaching the systemic circulation, cardiovascular and central nervous system derangements may appear, with potentially fatal complications if left untreated. The pillars for LAST treatment are advanced life support measures, airway and seizure management, and a 20% lipid emulsion intravenous administration. When occurring in the prehospital setting, LAST is difficult to recognize, mostly because of its features overlapping with other acute conditions. Prompt treatment is also challenging because lipid emulsion may not be routinely carried on emergency vehicles. This article reports a case of LAST occurring in a dental ambulatory located in a remote location within the Italian Alps in which effective communication among different components of the same regional health care system (dispatch center, prehospital teams, and hospital network) led to fast lipid emulsion retrieval en route and on-site toxicity resolution. This case can inspire future operational changes, such as antidote networks available to prehospital emergency medicine crews, avoiding unnecessary deployment of antidotes on ambulances or helicopters, which is difficult to preserve without increasing management costs. However, to be established, such a network would need protocols to facilitate antidote retrieval, training focused on toxidromes recognition, and improved communication skills among different professionals involved in prehospital emergency medicine.

Factors causing emergency medical care overload during heatwaves: A Delphi study.

Heatwaves pose an important risk for population health and are associated with an increased demand for emergency care. To find factors causing such overload, an online Delphi study included 15 experts in emergency medicine, disaster medicine, or public health. One open-ended question was delivered in the first round. After content analysis, the obtained statements were sent to the experts in two rounds to be rated on a 7-point linear scale. Consensus was defined as a standard deviation ≤ 1.0. Thirty-one statements were obtained after content analysis. The experts agreed on 18 statements, mostly focusing on the input section of patient processing and identifying stakeholders, the population, and primary care as targets of potential interventions. Additional dedicated resources and bed capacity were deemed important as per throughput and output sections, respectively. These findings could be used in the future to implement and test solutions to increase emergency healthcare resilience during heatwaves and reduce disaster risk due to climatic change.

Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes.

Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19. We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT). Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1_pre (basal level) and at T2_pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation.

Feasibility of chest ultrasound up to 42 m underwater.

After recent advancements, ultrasound has extended its applications from bedside clinical practice to wilderness medicine. Performing ultrasound scans in extreme environments can allow direct visualization of unique pathophysiological adaptations but can be technically challenging. This paper summarizes how a portable ultrasound apparatus was marinized to let scientific divers and sonographers perform ultrasound scans of the lungs underwater up to - 42 m. A metallic case protected the ultrasound apparatus inside; a frontal transparent panel with a glove allowed visualization and operation of the ultrasound by the diving sonographer. The inner pressure was equalized with environmental pressure through a compressed air tank connected with circuits similar to those used in SCUBA diving. Finally, the ultrasound probe exited the metallic case through a sealed aperture. No technical issues were reported after the first testing step and the real experiments.

Relative hypoxemia at depth during breath-hold diving investigated through arterial blood gas analysis and lung ultrasound.

Pulmonary gas exchange in breath-hold diving (BHD) consists of a progressive increase in arterial partial pressures of oxygen ([Formula: see text]) and carbon dioxide ([Formula: see text]) during descent. However, recent findings have demonstrated that [Formula: see text] does not consistently rise in all subjects. This study aimed at verifying and explaining [Formula: see text] derangements during BHD analyzing arterial blood gases and searching for pulmonary alterations with lung ultrasound. After ethical approval, 14 fit breath-hold divers were included. Experiments were performed in warm water (temperature: 31°C). We analyzed arterial blood gases immediately before, at depth, and immediately after a breath-hold dive to -15 m of fresh water (mfw) and -42 mfw. Signs of lung interstitial edema and atelectasis were searched simultaneously with a marinized lung ultrasound. In five subjects (-15 mfw) and four subjects (-42 mfw), the [Formula: see text] at depth seems to decrease instead of increasing. [Formula: see text] and lactate showed slight variations. At depth, no lung ultrasound alterations were seen except in one subject (hypoxemia and B-lines at -15 mfw; B-lines at the surface). Lung interstitial edema was detected in 3 and 12 subjects after resurfacing from -15 to -42 mfw, respectively. Two subjects developed hypoxemia at depth and a small lung atelectasis (a focal pleural irregularity of triangular shape, surrounded by thickened B-lines) after resurfacing from -42 mfw. Current experiments confirmed that some BH divers can experience hypoxemia at depth. The hypothesized explanation for such a discrepancy is lung atelectasis, which could not be detected in all subjects probably due to limited time available at depth.NEW & NOTEWORTHY During breath-hold diving, arterial partial pressure of oxygen ([Formula: see text]) and arterial partial pressure of carbon dioxide ([Formula: see text]) are believed to increase progressively during descent, as explained by theory, previous end-tidal alveolar gas measurements, and arterial blood gas analysis in hyperbaric chambers. Recent experiments in real underwater environment found a paradoxical [Formula: see text] drop at depth in some divers. This work confirms that some breath-hold divers can experience hypoxemia at depth. The hypothesized explanation for such a discrepancy is lung atelectasis, as suggested by lung ultrasound findings.

Comparison between Arterial Blood Gases and Oxygen Reserve Index™ in a SCUBA Diver: A Case Report.

Hypoxia and hyperoxia are both worrisome issues potentially affecting SCUBA divers, but validated methods to monitor these two conditions underwater are still lacking. In this experiment, a volunteer SCUBA diver was equipped with a pulse oximeter to detect peripheral oxygen saturation (SpO2) and a device to monitor the oxygen reserve index (ORi™). ORi™ values were compared with arterial blood oxygen saturation (SaO2) and the partial pressure of oxygen (PaO2) obtained from the cannulated right radial artery at three steps: at rest out of water; at -15 m underwater after pedaling on a submerged bike; after resurfacing. SpO2 and ORi™ mirrored the changes in SaO2 and PaO2, confirming the expected hyperoxia at depth. To confirm the potential usefulness of an integrated SpO2 and ORi™ device, further studies are needed on a broader sample with different underwater conditions and diving techniques.

Appropriateness of packed red blood cells transfusions in chronic anemic patients in the emergency department: the TRANSFUS-ED retrospective analysis.

Patients suffering from chronic anemia can benefit from scheduled transfusions of packed red blood cells (PRBCs), while urgent transfusions have specific indications. These patients frequently seek medical attention in the emergency department (ED), where they can be inappropriately transfused, but research in this field is limited. This study aimed to assess the appropriateness of PRBCs transfusions in chronic anemic patients in the ED. A retrospective analysis was performed on patients who accessed the ED of the Azienda Ospedaliera di Padova (Padova, Italy) between 2016 and 2019 and received PRBCs transfusions. Patients aged ≥ 18 years old and with chronic anemia were included, while those with acute anemia or admitted to the hospital after the transfusion were excluded. Chronic anemia was defined as satisfying one of the following in the past medical history: diagnosis of chronic anemia; two or more previous blood samplings demonstrating anemia; periodic transfusions. As primary outcome, the appropriateness of transfusions was assessed according to the American Association of Blood Banks (AABB) 2016 criteria, using the recommended threshold of 7 g/dL for hemodynamically stable adults and 8 g/dL for patients with pre-existing cardiovascular disease. Out of 1153 transfusions, 344 transfusions were included in the study. According to our criteria, 139 (40.4%) patients were inappropriately transfused, resulting in a total estimated cost of 54,528.71 € in the study period. This study showed that transfusions in chronic anemic patients are recurrent events in the ED and are frequently inappropriate. A possible explanation could be the lack of a well-structured primary care network granting periodic transfusions in ambulatory centers. In the future, implementing and improving chronic anemic patients' access to transfusion services through dedicated pathways could reduce the burden on the ED and also decrease costs.

Seasonal Oxy-Inflammation and Hydration Status in Non-Elite Freeskiing Racer: A Pilot Study by Non-Invasive Analytic Method.

Freeskiing is performed in an extreme environment, with significant physical effort that can induce reactive oxygen species (ROS) generation and dehydration. This study aimed to investigate the evolution of the oxy-inflammation and hydration status during a freeskiing training season with non-invasive methods. Eight trained freeskiers were investigated during a season training: T0 (beginning), T1-T3 (training sessions), and T4 (after the end). Urine and saliva were collected at T0, before (A) and after (B) T1-T3, and at T4. ROS, total antioxidant capacity (TAC), interleukin-6 (IL-6), nitric oxide (NO) derivatives, neopterin, and electrolyte balance changes were investigated. We found significant increases in ROS generation (T1A-B +71%; T2A-B +65%; T3A-B +49%; p < 0.05-0.01) and IL-6 (T2A-B +112%; T3A-B +133%; p < 0.01). We did not observe significant variation of TAC and NOx after training sessions. Furthermore, ROS and IL-6 showed statistically significant differences between T0 and T4 (ROS +48%, IL-6 +86%; p < 0.05). Freeskiing induced an increase in ROS production, which can be contained by antioxidant defense activation, and in IL-6, as a consequence of physical activity and skeletal muscular contraction. We did not find deep changes in electrolytes balance, likely because all freeskiers were well-trained and very experienced.

Dopamine/BDNF loss underscores narcosis cognitive impairment in divers: a proof of concept in a dry condition.

PURPOSE: Divers can experience cognitive impairment due to inert gas narcosis (IGN) at depth. Brain-derived neurotrophic factor (BDNF) rules neuronal connectivity/metabolism to maintain cognitive function and protect tissues against oxidative stress (OxS). Dopamine and glutamate enhance BDNF bioavailability. Thus, we hypothesized that lower circulating BDNF levels (via lessened dopamine and/or glutamate release) underpin IGN in divers, while testing if BDNF loss is associated with increased OxS. METHODS: To mimic IGN, we administered a deep narcosis test via a dry dive test (DDT) at 48 msw in a multiplace hyperbaric chamber to six well-trained divers. We collected: (1) saliva samples before DDT (T0), 25 msw (descending, T1), 48 msw (depth, T2), 25 msw (ascending, T3), 10 min after decompression (T4) to dopamine and/or reactive oxygen species (ROS) levels; (2) blood and urine samples at T0 and T4 for OxS too. We administered cognitive tests at T0, T2, and re-evaluated the divers at T4. RESULTS: At 48 msw, all subjects experienced IGN, as revealed by the cognitive test failure. Dopamine and total antioxidant capacity (TAC) reached a nadir at T2 when ROS emission was maximal. At decompression (T4), a marked drop of BDNF/glutamate content was evidenced, coinciding with a persisting decline in dopamine and cognitive capacity. CONCLUSIONS: Divers encounter IGN at - 48 msw, exhibiting a marked loss in circulating dopamine levels, likely accounting for BDNF-dependent impairment of mental capacity and heightened OxS. The decline in dopamine and BDNF appears to persist at decompression; thus, boosting dopamine/BDNF signaling via pharmacological or other intervention types might attenuate IGN in deep dives.

SARS-CoV-2 Contamination of Ambulance Surfaces and Effectiveness of Routine Decontamination Procedure: A Classic Hygiene Lesson for A Novel Pathogen.

The efficacy of standard operating procedures (SOPs) for the decontamination of ambulances against SARS-CoV-2 has been debated. In Italy, the differential use of ambulances was implemented by regional health authorities, with selected vehicles being used exclusively for transporting COVID-19 patients. We investigated the presence of SARS-CoV-2 on high-touch surfaces in ambulances to assess contamination dynamics and the effectiveness of decontamination SOPs. Four high-touch surfaces were sampled before and after decontamination (T0; T1). The gloves of the EMS crew chief were also sampled. RNA extraction was performed with a commercial kit, followed by RT-qPCR molecular detection of SARS-CoV-2. A total of 11 transports were considered. Seven transports had at least one positive sample; all were related to a COVID-19 patient. Three of the negative transports had dealt with COVID-19 case, and one had dealt with a COVID-19-negative patient. One door handle and one oxygen knob were positive at T0, with negative T1 swabs. The monitors were positive in 5 transports at T0, yet they were never positive at T1. Three stretcher handles tested positive at T0, and two of them also at T1, possibly having bypassed decontamination during personnel dismounting. Gloves were contaminated in five transports, in which 1 to 3 additional samples (monitor, knob, stretcher) resulted as positive. Overall, the efficacy of decontamination SOPs was confirmed under the unprecedented conditions of the COVID-19 emergency. However, the importance of correct hand-hygiene and glove-disposal should be further emphasized through the dedicated training of EMS personnel.

Effects of short-term unloading and active recovery on human motor unit properties, neuromuscular junction transmission and transcriptomic profile.

Electrophysiological alterations of the neuromuscular junction (NMJ) and motor unit potential (MUP) with unloading are poorly studied. We aimed to investigate these aspects and the underlying molecular mechanisms with short-term unloading and active recovery (AR). Eleven healthy males underwent a 10-day unilateral lower limb suspension (ULLS) period, followed by 21-day AR based on resistance exercise. Quadriceps femoris (QF) cross-sectional area (CSA) and isometric maximum voluntary contraction (MVC) were evaluated. Intramuscular electromyographic recordings were obtained during 10% and 25% MVC isometric contractions from the vastus lateralis (VL). Biomarkers of NMJ molecular instability (serum c-terminal agrin fragment, CAF), axonal damage (neurofilament light chain) and denervation status were assessed from blood samples and VL biopsies. NMJ and ion channel transcriptomic profiles were investigated by RNA-sequencing. QF CSA and MVC decreased with ULLS. Increased CAF and altered NMJ transcriptome with unloading suggested the emergence of NMJ molecular instability, which was not associated with impaired NMJ transmission stability. Instead, increased MUP complexity and decreased motor unit firing rates were found after ULLS. Downregulation of ion channel gene expression was found together with increased neurofilament light chain concentration and partial denervation. The AR period restored most of these neuromuscular alterations. In conclusion, the human NMJ is destabilized at the molecular level but shows functional resilience to a 10-day unloading period at least at relatively low contraction intensities. However, MUP properties are altered by ULLS, possibly due to alterations in ion channel dynamics and initial axonal damage and denervation. These changes are fully reversed by 21 days of AR. KEY POINTS: We used integrative electrophysiological and molecular approaches to comprehensively investigate changes in neuromuscular integrity and function after a 10-day unilateral lower limb suspension (ULLS), followed by 21 days of active recovery in young healthy men, with a particular focus on neuromuscular junction (NMJ) and motor unit potential (MUP) properties alterations. After 10-day ULLS, we found significant NMJ molecular alterations in the absence of NMJ transmission stability impairment. These findings suggest that the human NMJ is functionally resilient against insults and stresses induced by short-term disuse at least at relatively low contraction intensities, at which low-threshold, slow-type motor units are recruited. Intramuscular electromyography analysis revealed that unloading caused increased MUP complexity and decreased motor unit firing rates, and these alterations could be related to the observed changes in skeletal muscle ion channel pool and initial and partial signs of fibre denervation and axonal damage. The active recovery period restored these neuromuscular changes.

Delayed Neurological Sequelae Successfully Treated with Adjuvant, Prolonged Hyperbaric Oxygen Therapy: Review and Case Report.

Carbon Monoxide (CO) intoxication is still a leading cause of mortality and morbidity in many countries. Due to the problematic detection in the environment and subtle symptoms, CO intoxication usually goes unrecognized, and both normobaric and hyperbaric oxygen (HBO) treatments are frequently administered with delay. Current knowledge is mainly focused on acute intoxication, while Delayed Neurological Sequelae (DNS) are neglected, especially their treatment. This work details the cases of two patients presenting a few weeks after CO intoxication with severe neurological impairment and a characteristic diffused demyelination at the brain magnetic resonance imaging, posing the diagnosis of DNS. After prolonged treatment with hyperbaric oxygen, combined with intravenous corticosteroids and rehabilitation, the clinical and radiological features of DNS disappeared, and the patients' neurological status returned to normal. Such rare cases should reinforce a thorough clinical follow-up for CO intoxication victims and promote high-quality studies.

Knowledge Gaps and Research Priorities on the Health Effects of Heatwaves: A Systematic Review of Reviews.

Although extreme weather events have played a constant role in human history, heatwaves (HWs) have become more frequent and intense in the past decades, causing concern especially in light of the increasing evidence on climate change. Despite the increasing number of reviews suggesting a relationship between heat and health, these reviews focus primarily on mortality, neglecting other important aspects. This systematic review of reviews gathered the available evidence from research syntheses conducted on HWs and health. Following the PRISMA guidelines, 2232 records were retrieved, and 283 reviews were ultimately included. Information was extracted from the papers and categorized by topics. Quantitative data were extracted from meta-analyses and, when not available, evidence was collected from systematic reviews. Overall, 187 reviews were non-systematic, while 96 were systematic, of which 27 performed a meta-analysis. The majority evaluated mortality, morbidity, or vulnerability, while the other topics were scarcely addressed. The following main knowledge gaps were identified: lack of a universally accepted definition of HW; scarce evidence on the HW-mental health relationship; no meta-analyses assessing the risk perception of HWs; scarcity of studies evaluating the efficacy of adaptation strategies and interventions. Future efforts should meet these priorities to provide high-quality evidence to stakeholders.