Limited Blood Flow Research Articles

Amyloid Beta Peptides and Th1 Cytokines Modulate Human Brain Vascular Smooth Muscle Tonic Contractile Capacity In Vitro: Relevance to Alzheimer's Disease?

Alzheimer’s Disease (AD) is a neurodegenerative condition characterized both by the presence of tau protein neurofibrillary tangles and amyloid beta (Aβ) containing extracellular “plaques”. The cleavage of amyloid precursor protein (APP) yields several Aβ peptides. Although Aβ toxicity to neurons has been described extensively, its effects on other components of the neurovasculature such as vascular smooth muscle cells have been less well characterized. AD is now also recognized as a neurovascular disease characterized by cerebral microbleeds and disturbances in autoregulation. AD is also a neuroinflammatory condition in which several proinflammatory cytokines are elevated and may contribute to the intensification of AD severity. Cerebral autoregulation (the mechanism by which brain blood flow is maintained despite changes in perfusion pressure) is extremely tightly controlled in the brain and shows disturbances in AD. The failure of autoregulation in AD may make the brain susceptible to cerebral microbleeds through a reduced capacity to limit blood flow when pressure is increased. Conversely, reduced vasodilation during low flow might could also exacerbate tissue hypoxia. Currently, whether and how Aβ peptides and inflammatory cytokines depress brain smooth muscle cell tonic contraction is not known, but could reveal important targets in the preservation of autoregulation which is disturbed in AD. We used a collagen gel contractility assay to evaluate the influence of Aβ25-35, Aβ1-40 and Aβ1-42 peptides and inflammatory cytokines on the tonic contractility of human brain vascular smooth muscle cells (HBVSMC) as an in vitro model of cerebral autoregulation. We found that 5 and 10 μM Aβ1-42 significantly depressed HBVSM contractility, while Aβ1-40 5–20 μM had no effect on contractility. Conversely, Aβ25-35 (1–50 μM) increased contractility. Interestingly, the inflammatory cytokines TNF-α (20 ng/mL), IL-1β (20 ng/mL) and IFN-γ (1000 U/mL) also depressed HBVSM tonic contractility alone and in combination. These data suggest that both the inflammatory milieu in AD as well as the abundance of Aβ peptides may promote autoregulatory failure and increase brain susceptibility to dysregulated perfusion and microbleeds which are an important and devastating characteristic of AD.

Pediatric Extracorporeal Cardiopulmonary Resuscitation ELSO Guidelines.

Pediatric Extracorporeal Cardiopulmonary Resuscitation ELSO Guidelines.

Design Considerations for Coronary Stents and their Efficacy: A Review.

Cardiovascular disease (CVD), referring to a group of diseases that inhibit the function of the heart or blood vessels, is the number one cause of death in the world. The largest subset of CVD is coronary heart disease (CHD), which is damage or disease to the heart's coronary arteries, usually caused by the buildup of atherosclerotic plaque over time along the walls of the coronary arteries. Such plaques can rupture, forming thrombi inside the arteries and limiting blood flow to the myocardium, thus leading to myocardial infarction (MI) and/or death. Coronary stents, together with balloon angioplasty, have so far been used extensively in percutaneous coronary intervention (PCI) to re-open blocked arteries and combat CHD. Since their introduction, the design of coronary stents has evolved significantly, with there today being many competing stent product types and products on the market. Each stent has a unique design with differing features, and it is the combination of such design choices that overall helps determine a coronary stent's safety and efficacy in treating CHD. This paper presents a review of the design considerations of coronary stents and their related clinical efficacy, focusing on developments over the past three years.

Morphofunctional changes and expression of LAMP2 in the rat hippocampus in chronic cerebral ischemia

AbstractBackgroundThe hippocampus, part of the limbic system, is involved in the formation of the cognitive sphere and is one of the most vulnerable structures in chronic cerebral ischemia.MethodChronic cerebrovascular disorders modeled in rats by limiting blood flow with applying ligatures to the carotid arteries. Behavioral status, cognitive and mnemonic functions, the degree of neuronal damage, and the level of LAMP2 expression in the pyramidal layer of the hippocampus were investigated.ResultAfter a 20‐day subtotal cerebral ischemia, we revealed a change in the functional state of the nervous system, expressed in a decrease of the main reflexes, tentative‐research activity, as well as a decrease in memory. Dystrophic changes in pyramidal neurons were of different severity, determined by a significant increase in the number of hyperchromic neurons, and in most of them total nuclear and cytoplasmic hyperchromia was observed, combined with a picture of spongiosis due to pericellular edema. A significant increase in LAMP2 expression compared to the control in both the relative area by 0.8% (p <0.05) and the intensity of the expression was detected in the CA1 zone.ConclusionThe amplification of LAMP‐2 expression is a marker for the inclusion of autophagy mechanisms aimed at implementing compensatory processes in many disorders of the central nervous system, including chronic cerebral ischemia. The observed increase in the specific number of pyramidal neurons with signs of damage, sharp pericellular and perivascular edema in combination with increased expression of LAMP‐2 in the CA1 zone of the hippocampus indicates the important role of autophagy for the survival of neurons in chronic cerebral ischemia.

Bone biochemical marker response to a plyometric exercise session with and without blood flow restriction in inactive adolescent females

Background and Aims: Physical activity and blood flow restriction (BFR) training can affect bone metabolism. This study aimed to investigate the effect of a plyometric exercise session with and without blood flow restriction on bone metabolism markers, such as bone alkaline phosphatase (BALP) and C-terminal telopeptide of type 1collagen (CTX), as the markers of bone formation and destruction, respectively, among inactive adolescent females. Materials and Methods: This study was conducted using a quasi-experimental design with pretest-posttest. The participants (n=48) were randomly divided into four groups of high-intensity training (n=12), low-intensity training (n=12), low-intensity training+restricted blood flow (n=12), and control (n=12). The training protocol included 68 jumping movements. The intensity of the exercise was less than two and more than four times the body weight for low intensity groups with and without obstruction and the high-intensity group, respectively. Blood samples were taken before and immediately after the exercise to evaluate BALP and CTX. Data analysis was performed using dependent t-test and one-way ANOVA. A p-value of ≤0.05 was considered statistically significant. Results: A significant decrease was observed in CTX serum levels in high-intensity exercise group (P=0.04) and low-intensity exercise group with limited blood flow (P=0.03), compared to those in the pre-test. However, there was no significant within-group and intergroup changes in serum levels of bone formation marker (P≥0.05). Conclusion: According to the results, a low-intensity plyometric exercise session with blood BFR can be as effective as high-intensity plyometric exercises in altering bone metabolism (reducing bone absorption marker).

More than a matter of the heart: the concept of intravascular multimorbidity in cardiac rehabilitation

ABSTRACT Introduction Coronary artery disease (CAD) is the major cause of death of cardiovascular disease. It is initiated by atherosclerosis, which narrows the coronary arteries and limits blood flow and oxygen to the heart. Multiple pathophysiological conditions within the arteries, such as arterial wall thickening, endothelial dysfunction, and arterial stiffening, are associated with the development of atherosclerosis. Areas covered We introduce a new concept of ‘intravascular multimorbidity,’ the presence and integration of multiple pathophysiological conditions within the arteries. We also introduce some measurements of intravascular multimorbidity and discuss how these measurements can be utilized in cardiac rehabilitation (CR). Expert opinion We propose that the measures of intravascular multimorbidity in different arteries may provide information on disease severity and serve as unique prognostic ‘barometers’ to disease progression in patients with CAD. By measuring the underlying disease mechanisms within the arteries and understanding individual variability of disease progression/regression, these measures may also provide a unique prognostic window in CR. The window into intravascular multimorbidity can help guide clinical strategies, for example, assessing progress and appropriate titration of exercise. Intravascular multimorbidity may represent an important opportunity for more researchers and clinical professions to evaluate patients in CR.

A non-invasive continuous cuffless blood pressure estimation using dynamic Recurrent Neural Networks

Cardiovascular diseases (CVD) have become the most important health problem of our time. High blood pressure, which is cardiovascular disease, is a risk factor for death, stroke, and heart attack. Blood pressure measurement is commonly used to limit blood flow in the arm or wrist, with the cuff. Since blood pressure cannot be measured continuously in this method, the dynamics underlying blood pressure cannot be determined and are inefficient in capturing symptoms. This paper aims to perform blood pressure estimation using Photoplethysmography (PPG) and Electrocardiography (ECG) signals that do not obstruct the vascular access. These signals were filtered and segmented synchronously from the R interval of the ECG signal, and chaotic, time, and frequency domain features were subtracted, and estimation methods were applied. Different methods of machine learning in blood pressure estimation are compared. Dynamic learning methods such as Recurrent Neural Network (RNN), Nonlinear Autoregressive Network with Exogenous Inputs Neural Networks NARX-NN and Long-Short Term Memory Neural Network (LSTM-NN) used. Estimation results have been evaluated with performance criteria. Systolic Blood Pressure (SBP) error mean ± standard deviation = 0.0224 ± (2.211), Diastolic Blood Pressure (DBP) error mean ± standard deviation = 0.0417 ± (1.2193) values have been detected in NARX artificial neural network. The blood pressure estimation results are evaluated by the British Hypertension Society (BHS) and American National Standard for Medical Instrumentation ANSI/AAMI SP10: 2002. Finding the most accurate and easy method in blood pressure measurement will contribute to minimizing the errors.

Critical coarctation of the aorta: diagnostic capabilities and methods of surgical treatment of aortic coarctation in newborns

Critical coarctation of the aorta in newborns usually presents with severe narrowing of the cavotricuspid isthmus and space adjacent to the arterial duct, limiting blood flow to the thoracic aorta. Patient survival depends on duct patency. Rapid deterioration and development of multiple organ failure usually result from spontaneous closure of the patent arterial duct. This deterioration is due in part to reduced renal perfusion and results in fluid and acid retention, causing heart failure and metabolic acidosis. This may be alleviated by the administration of intravenous prostaglandin E1, with a temporary improvement in distal aortic blood flow and the overall condition of the patient. Primary repair is associated with a high risk of unfavourable outcomes due to severe systemic outflow obstruction and multiple organ failure. Therefore, as a bridge to subsequent radical surgery, palliative stenting is the preferred method in newborns with critical aortic coarctation in the decompensated state.Received 16 January 2020. Revised 29 March 2020. Accepted 30 March 2020.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Author contributionsConception and design: S.M. Ivantsov, A.V. Voitov, Yu.Yu. KulyabinDrafting the article: K.A. RzaevaCritical revision of the article: I.A. Soynov, A.V. Gorbatykh, Yu.N. Gorbatykh, A.V. Bogachev-ProkophievFinal approval of the version to be published: K.A. Rzaeva, I.A. Soynov, A.V. Gorbatykh, Yu.Yu. Kulyabin, A.V. Voitov, S.M. Ivantsov, Yu.N. Gorbatykh, A.V. Bogachev-Prokophiev

Peripheral Revascularization Reverses The Decline In Active Muscle Oxygen Saturation In Peripheral Artery Disease

Peripheral artery disease (PAD) is a progressive atherosclerotic disease that limits blood flow to the skeletal muscles in the lower extremity. Reductions in blood flow may be more pronounced during ambulation or exercise and produce leg cramping or pain known as intermittent claudication. Recent studies have shown an exaggerated blood pressure response with lower muscle oxygen saturation (SmO2) during foot exercise in patients with PAD. However, it is unclear whether surgical and/or endovascular interventions normalize this response. PURPOSE: To examine whether revascularization procedures improve calf muscle SmO2 and reduce blood pressure responses during dynamic foot exercise in patients with PAD. We hypothesized that revascularization would improve SmO2 responses (indicating greater tissue perfusion) and that the blood pressure response would be attenuated during exercise. METHODS: Patients with symptomatic PAD (n = 6) performed incremental supine plantar flexion exercise, starting at 0.5 kg and increased by 0.5 kg every minute for up to 6 minutes, pre- and one-month post peripheral revascularization procedure. SmO2 was measured continuously from the gastrocnemius muscle, while heart rate and blood pressure were measured beat-by-beat. RESULTS: Reductions in SmO2 from baseline to end-exercise were attenuated post-revascularization (-6.5 ± 6.2% vs. -39.8 ± 22.5%, P < .05). The change in mean arterial blood pressure was reduced post-revascularization (4 ± 4 mmHg vs. 16 ± 12 mmHg P < .05). PAD patients exercised longer post-revascularization (5.8 ± 0.4 min vs. 4.0 ± 1.5 min P < .05). CONCLUSIONS: These data suggest that revascularization lessens the degree and rapidity of decline in SmO2 during exercise, and lowers the exaggerated blood pressure response in patients with PAD. Supported by NIH Grant P01 HL134609

Visualization of the consequences of Succinate Dehydrogenase Inhibition on Oxygen utilization During Hemorrhagic Shock using Hyperspectral Imaging

IntroductionHemorrhagic shock (HS) results in reduced pressure, limited blood flow, and inadequate oxygen delivery to maintain cellular function. Reduced microcirculatory blood flow results in ischemia, as the tissue is no longer properly perfused or oxygenated. During resuscitation from HS, reperfusion promotes the formation of reactive oxygen species (ROS) as a byproduct of the Krebs cycle. Itaconate limits formation of ROS generated during reperfusion by inhibiting succinate dehydrogenase (SDH) activity, thus limiting tissue and organ damage. Hyperspectral Imaging (HSI) can be used to interrogate hemoglobin oxygen (HbO2) saturation in microvessels. Thus, the objective of this study was to use HSI to monitor changes in oxygen utilization within the microcirculation during resuscitation from HS with itaconate pretreatment.Materials and MethodsGolden Syrian hamsters were instrumented with a dorsal window chamber. A Resonon Pika‐L (Resonon, Bozeman, MT, USA) bench top HSI system was used. Each image was fitted with a Spatial mean filter and Savitzky‐Golay filter to decrease scatter noise, and a vessel mask was applied based on an intensity threshold to remove tissue from blood vessels. Spectral rescaling and a linear least squares fit were used to provide abundance of Hb and HbO2. Hemorrhage was induced by withdrawing 50% of the animal’s blood volume (BV, estimated as 7% of body weight) over 10 minutes. During hemorrhage and shock, images were taken continuously using a custom Python algorithm controlling the camera and illumination with a custom build relay. Before fluid resuscitation, itaconate was administered. Fluid resuscitation was accomplished by infusion of 25% of the animal’s BV of HEXTEND® (6% Hetastarch in Lactated Electrolyte Injection. Hospira Inc, Lake Forest, IL). The animal was resuscitated over 10 minutes and images taken every minute. Recovery was monitored over a period of 1 hour with images taken every 5 minutes.Results and DiscussionIncreasing doses of itaconate restored HbO2 saturation in venules, which confirms the inhibition of SDH by itaconate. Itaconate limits oxygen consumption of the tissues, preventing the formation of ROS in tissue during reperfusion, as indicated by higher levels of venular O2 saturation. However, these effects are only temporary as the HbO2 saturation levels taper off over time.ConclusionsIn conclusion, the inhibition of SDH with itaconate lead to the accumulation of succinate, limited tissue oxygen utilization, and prevented the formation of ROS during reperfusion. With further research, itaconate could potentially help to reduce reperfusion sequalae post treatment of trauma injuries, surgery, and combat casualties. In future studies, we aim to administer itaconate as an additive to the resuscitation fluid with the goal of evaluating the long‐term implications of preventing reperfusion injury.Support or Funding InformationThis study was supported by NIH NHLBI R01HL126945 and R01HL138116.

A Massage Did What?

Internal Carotid Artery (ICA) dissection is a condition that occurs when a layer of the arterial wall begins to tear which may form a clot that limits blood flow. It is characterized by pain over the head, face or neck. Some may present with pulsatile tinnitus or visual disturbances. It is an uncommon cause of ischemic stroke that can occur in the setting of trauma or even spontaneously. It is usually related to an underlying connective tissue disease such as, Marfan or Ehlers-Danlos. But it can also present in those with fibromuscular dysplasia or atherosclerosis. Here we present a case of ICA dissection following manual manipulation.

Abstract TP436: MyRIAD Mechanisms of Recurrent Stroke in Intracranial Atherosclerotic Disease

Background: The NINDS-funded Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study used a battery of MRI and TCD techniques to discern key pathophysiology leading to a relatively high rate of recurrent stroke. Our study objectives aimed to relate imaging abnormalities of limited arterial blood flow, distal tissue perfusion and artery-to-artery emboli with new infarcts on 6-8 week MRI. Methods: MyRIAD is a prospective, multicenter, observational study of patients with recent (&lt;21 days) ischemic stroke or TIA due to 50-99% ICAD. Quantitative MRA (QMRA), perfusion MRI and TCD vasomotor reactivity (VMR) with emboli detection (ED) were acquired at enrollment. Central adjudication of each imaging modality, clinical events and 6-8 week MRI were independently ascertained. Results: MyRIAD enrolled 105 (mean age 63.7 years, SD 11.8 years; 43% women) patients. Primary outcomes of recurrent stroke in the territory occurred in 9/105 (9%) with secondary outcomes of territorial TIA in 7/105 (7%) and new infarcts on 6-8 week MRI in 22/87 (25%). The limited number of clinical stroke and TIA endpoints precluded definitive analysis of mechanism. Pre-specified Tmax&gt;4s 10 cc lesions on perfusion MRI were noted in 40/92 (43%) but did not predict new infarcts at 6-8 week MRI. New infarcts were noted in 12/44 (27%) of those with Tmax&gt;4s 5 cc lesions at baseline compared to 3/26 (12%) when absent. Abnormal volume flow ratio (VFR) on QMRA was noted in 25/98 (26%), abnormal TCD VMR in 25/76 (33%) and ED in 30/74 (41%). Other pre-specified analyses revealed both abnormal VMR and ED in 21/77 (27%) and both abnormal Tmax&gt;4s perfusion and VFR in 16/99 (16%). Two or more imaging abnormalities were noted at baseline in 49/105 (47%) and stenosis ≥ 70% in 76/91 (84%). New infarcts on 6-8 week MRI were more frequent with ≥ 2 abnormalities (33 vs 18%, p=0.1) and ≥ 70% stenosis (29 vs 7%, p=0.2). Conclusions: Early, recurrent infarction on MRI is common in ICAD. Imaging abnormalities of limited arterial blood flow or distal tissue perfusion and artery-to-artery emboli are frequent and the presence of multiple abnormalities may increase risk. Larger ICAD studies are needed to link routinely acquired imaging with covert infarcts and cognitive impairment.

Towards virtual surgery planning: the modified Blalock-Taussig Shunt

A modified Blalock-Taussig shunt (MBTS) is an aortopulmonary shunt to establish or augment pulmonary perfusion in congenital cardiac defects with limited pulmonary blood flow. Proper function of this shunt is of utmost importance. In clinical practice, prediction of flow in an MBTS relies on previous experience. In the research field, computational modeling techniques have been developed to simulate flow in an MBTS and predict its performance. These techniques are promising but also time consuming and prone to uncertainties; therefore not yet suitable for clinical practice. Here we present a simplified, patient-based computational model to predict mean circulatory flow characteristics after MBTS insertion. Simulations performed over a range of pulmonary vascular resistances, were compared to data from: i) previous modeling studies; ii) data from the specific patient modeled, and iii) a cohort of patients with MBTS. Model predictions were within one standard deviation from cohort data; and within 1% from results of previous (more complex) computational models. In comparison to previous studies, our model is computationally stable with significantly shorter computational time to perform simulations. We envision that our approach could be used in the future to perform virtual surgeries, quickly testing different surgical scenarios using the patient own geometrical and physiological characteristics, to aid surgeons in decision making.

Association Between Cognitive Function And Funcional Capacity Of Patients With Peripheral Artery Disease

INTRODUTION: Patients with peripheral arterial disease (PAD) and symptoms of intermittent claudication present reduced mobility and decreased ability to exercise activities of daily living due to atherosclerotic plaques in the lower limbs that limit blood flow to the muscles. Because it is a systemic disease, PAD has been associated with cognitive decline, however, as far as functional impairment is related to cognitive impairment is still uncertain. PURPOSE: To analyze the association of cognitive function with the overall functional capacity and fragmented in three factors: (walking speed, muscle strength and balance) of patients with PAD. METHODS: Two hundred and nineteen patients with PAD and symptoms of intermittent claudication were submitted to the MoCA test to evaluate cognitive function. Functional ability was assessed by the Short Physical Performance Battery consisting of balance tests, sit-up and stand-up tests, and 4-meter walk test. For analysis of the associations, the binary logistic analysis was used, using the sex and age adjustment of the patients. RESULTS: There was no association between MoCA and sit-up (OR = -0.099, P = 0.780) as well as the test and balance (OR = -0.084, P = 0.832). The MoCA score was associated with performance on the test regardless of gender and age (OR = 1.186, P = 0.007). Despite the non-association in the first two tests, we found that cognitive function is associated with walking capacity. CONCLUSION: The cognitive function is associated with the ability to mobility in patients with PAD, based on these results we can assume that individuals physically active, yet affected by the disease, can slow cognitive decline.

Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator.

Constrictive vascular remodeling limiting blood flow, as well as compensatory outward remodeling, has been observed in many cardiovascular diseases; however, the underlying mechanisms regulating the remodeling response of the vessels remain unclear. Plasminogen activators (PA) are involved in many of the processes of vascular remodeling. We have shown previously that increased levels of tissue-type PA (tPA) contributes to outward vascular remodeling. To elucidate the mechanisms involved in the induction of outward remodeling we characterized changes in the expression profiles of 8799 genes in injured rat carotid arteries 1 and 4 days after recombinant tPA treatment compared to vehicle. Periadventitial tPA significantly increased lumen size and vessel area, encompassed by the external elastic lamina, at both one and 4 days after treatment. Among 41 differentially expressed known genes 1 day after tPA application, five genes were involved in gene transcription, five genes were related to the regulation of vascular tone [for example, thromboxane A2 receptor (D32080) or non-selective-type endothelin receptor (S65355)], and eight genes were identified as participating in vascular innervation [for example, calpain (D14478) or neural cell adhesion molecule L1 (X59149)]. Four days after injury in tPA-treated arteries, four genes, regulating vascular tone, were differentially expressed. Thus, tPA promotes outward arterial remodeling after injury, at least in part, by regulating expression of genes in the vessel wall related to function of the nervous system and vascular tone.

Abstract TP136: Mitochondrial Mechanisms of Resilience Revealed by Arctic Ground Squirrel Neural Cells

Arctic ground squirrels (AGS) are extreme hibernators capable of withstanding months of freezing temperatures. Curiously, AGS do not experience ischemic or reperfusion injuries despite limited cardiac output and cerebral blood flow during hibernation. Indeed, in simulated stroke or cardiac arrest, AGS also demonstrate marked resilience independent of the season or metabolic state of the animal. We found that AGS neuronal stem and progenitor cells (NSC/NPCs) demonstrate dramatic tolerance to multiple mitochondrial insults including oxygen glucose deprivation, rotenone treatment (Complex I inhibition), or FCCP treatment (uncoupling agent) in vitro. We sought to characterize the mitochondrial adaptations mediating this resilient phenotype. The AGS resilient phenotype is associated with altered mitochondrial dynamic regulation of fusion/fission and reduced oxidative metabolism. Overexpression of key AGS nuclear-encoded mitochondrial subunits such as Cox7a2l in mouse NSC/NPCs recapitulated the resilient phenotype and mitochondrial morphological and functional changes. AGS mitochondrial proteins are uniquely adapted to withstand metabolic stressors and contribute to the ability of AGS to dynamically regulate mitochondrial function. Development of therapeutic agents targeting mitochondrial structural properties may induce a protective phenotype and promote neuronal survival in patients with acute stroke.

Resuscitative endovascular balloon occlusion of the aorta (REBOA): a scoping review protocol concerning indications—advantages and challenges of implementation in traumatic non-compressible torso haemorrhage

IntroductionHaemorrhage remains the leading cause of preventable death in trauma. Damage control measures applied to patients in extremis in order to control exsanguinating bleeding from non-compressible torso injuries use different...

Adolescent Mental Health and the Choking Game.

To examine the demographic and health risk factors associated with participation in the choking game (CG), a dangerous and potentially fatal strangulation activity in which pressure is applied to the carotid artery to temporarily limit blood flow and oxygen. We obtained data from 2 cross-sectional studies realized respectively in 2009 and 2013 among French middle school students. The 2009 (n = 746) and 2013 (n = 1025) data sets were merged (N = 1771), and multivariate modeling was conducted to examine demographic and clinical characteristics of youth reporting a lifetime participation in the CG. The 2 studies included questions about risk-taking behaviors and substance use, and standardized assessments were used to collect conduct disorder symptoms and depressive symptoms. In the merged 2009 and 2013 data set, the lifetime prevalence of CG participation was 9.7%, with no statistically significant differences between boys and girls. A multivariate logistic regression revealed that higher levels of conduct disorder symptoms (odds ratio: 2.33; P < .001) and greater rates of depressive symptoms (odds ratio: 2.18; P < .001) were both significantly associated with an increased likelihood of reporting CG participation. The significant relationship between elevated levels of depressive symptoms and participation in the CG sheds new light on the function of self-asphyxial activities. However, with the finding that higher rates of conduct disorder symptoms were the most important predictor of CG participation, it is suggested that the profile and the underlying motivations of youth who engage in this activity should be reexamined.

Formula feeding and immature gut microcirculation promote intestinal hypoxia, leading to necrotizing enterocolitis.

ABSTRACTMajor risk factors for necrotizing enterocolitis (NEC) are formula feeding and prematurity; however, their pathogenic mechanisms are unknown. Here, we found that insufficient arginine/nitric oxide synthesis limits blood flow in the intestinal microvasculature, leading to hypoxia, mucosal damage and NEC in the premature intestine after formula feeding. Formula feeding led to increased intestinal hypoxia in pups at postnatal day (P)1 and P5, but not in more mature pups at P9. Accordingly, blood flow in the intestinal microvasculature increased after formula feeding in P9 pups only. mRNA profiling revealed that regulators of arginine/nitric oxide synthesis are at higher levels in endothelial cells of the intestine in P9 than in P1 pups. Importantly, arginine supplementation increased intestinal microvasculature blood flow and prevented NEC, whereas an arginine antagonist exacerbated NEC. Our results suggest that balancing intestinal oxygen demand and supply in the premature intestine by modulating arginine/nitric oxide could be used to prevent NEC.This article has an associated First Person interview with the first author of the paper.

From the Literature

From the Literature