Pulse Pressure and Acute Brain Injury in Venoarterial Extracorporeal Membrane Oxygenation: An Extracorporeal Life Support Organization Registry Analysis.

Low pulse pressure (PP) in venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is a marker of cardiac dysfunction and has been associated with acute brain injury (ABI) as continuous-flow centrifugal pump may lead to endothelial dysregulation. We retrospectively analyzed adults (≥18 years) receiving "peripheral" VA-ECMO for cardiogenic shock in the Extracorporeal Life Support Organization Registry (January 2018-July 2023). Acute brain injury (our primary outcome) included central nervous system (CNS) ischemia, intracranial hemorrhage, brain death, and seizures. Multivariable logistic regressions were performed to examine whether PP ≤10 mm Hg was associated with ABI. Of 9,807 peripheral VA-ECMO patients (median age = 57.4 years, 67% = male), 8,294 (85%) had PP >10 mm Hg versus 1,513 (15%) had PP ≤10 mm Hg. Patients with PP ≤10 mm Hg experienced ABI more frequently versus PP >10 mm Hg (15% versus 11%, p < 0.001). After adjustment, PP ≤10 mm Hg was independently associated with ABI (adjusted odds ratio [aOR] = 1.25, 95% confidence interval [CI] = 1.06-1.48, p = 0.01). Central nervous system ischemia and brain death were more common in patients with PP ≤10 versus PP >10 mm Hg (8% versus 6%, p = 0.008; 3% versus 1%, p < 0.001). Pulse pressure ≤10 mm Hg was associated with CNS ischemia (aOR = 1.26, 95% CI = 1.02-1.56, p = 0.03) but not intracranial hemorrhage (aOR = 1.14, 95% CI = 0.85-1.54, p = 0.38). Early low PP (≤10 mm Hg) at 24 hours of ECMO support was associated with ABI, particularly CNS ischemia, in peripheral VA-ECMO patients.

Completing the Puzzle: A Cluster of Hunting Dogs with Tick-Borne Illness from a Fishing Community in Tobago, West Indies.

Eight hunting dogs were visited by a state veterinarian on the island of Tobago, Trinidad and Tobago, West Indies, as owners reported anorexia and paralysis in five of their dogs. The veterinarian observed a combination of clinical signs consistent with tick-borne illness, including fever, anorexia, anaemia, lethargy and paralysis. Blood and ticks were collected from each dog and submitted to a diagnostic laboratory for analysis. Microscopic analysis revealed a mixed infection of intracytoplasmic organisms consistent with Babesia spp. (erythrocyte) and Ehrlichia spp. (monocyte), respectively, from one dog, while a complete blood count indicated a regenerative anaemia (n = 1; 12.5%), non-regenerative anaemia (n = 4; 50%), neutrophilia (n = 3; 37.5%), lymphocytosis (n = 2; 25%), thrombocytopaenia (n = 3; 37.5%) and pancytopaenia (n = 1; 12.5%). DNA isolated from the eight blood samples and 20 ticks (16 Rhipicephalus sanguineus and 4 Amblyomma ovale) were subjected to conventional PCR and next-generation sequencing of the 16S rRNA and 18S rRNA gene for Anaplasma/Ehrlichia and Babesia/Theileria/Hepatozoon, respectively. The DNA of Ehrlichia spp., closely related to Ehrlichia canis, was detected in the blood of three dogs (37.5%), Anaplasma spp., closely related to Anaplasma marginale, in two (25%), Babesia vogeli in one dog (12.5%) and seven ticks (35%) and Hepatozoon canis and Anaplasma spp., in one tick (5%), respectively. These findings highlight the need to test both the vector and host for the presence of tick-borne pathogens when undertaking diagnostic investigations. Further studies are also warranted to elucidate the susceptibility of canids to Anaplasma marginale.

Impact of Pulse Pressure on Acute Brain Injury in Venoarterial ECMO Patients with Cardiogenic Shock During the First 24 Hours of ECMO Cannulation: Analysis of the Extracorporeal Life Support Organization Registry.

Background: Low pulse pressure (PP) in venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is a marker of cardiac dysfunction and has been associated with acute brain injury (ABI) as continuous-flow centrifugal pump may lead to endothelial dysregulation. Methods: We retrospectively analyzed adults (≥18 years) on "peripheral" VA-ECMO support for cardiogenic shock in the Extracorporeal Life Support Organization Registry (1/2018-7/2023). Cubic splines were used to establish a threshold (PP≤10 mmHg at 24 hours of ECMO support) for "early low" PP. ABI included central nervous system (CNS) ischemia, intracranial hemorrhage, brain death, and seizures. Multivariable logistic regressions were performed to examine whether PP≤10 mmHg was associated with ABI. Covariates included age, sex, body mass index, pre-ECMO variables (temporary mechanical support, vasopressors, cardiac arrest), on-ECMO variables (pH, PaO2, PaCO2), and on-ECMO complications (hemolysis, arrhythmia, renal replacement therapy). Results: Of 9,807 peripheral VA-ECMO patients (median age=57.4 years, 67% male), 8,294 (85%) had PP>10 mmHg vs. 1,513 (15%) had PP≤10 mmHg. Patients with PP≤10 mmHg experienced ABI more frequently vs. PP>10 mmHg (15% vs. 11%, p<0.001). After adjustment, PP≤10 mmHg was independently associated with ABI (adjusted odds ratio [aOR]=1.25, 95% confidence interval [CI]=1.06-1.48, p=0.01). CNS ischemia and brain death were more common in patients with PP≤10 mmHg vs. PP>10 mmHg (8% vs. 6%, p=0.008; 3% vs. 1%, p<0.001). PP≤10 mmHg was associated with CNS ischemia (aOR=1.26, 95%CI=1.02-1.56, p=0.03) but not intracranial hemorrhage (aOR=1.14, 95%CI=0.85-1.54, p=0.38). Conclusions: Early low PP (≤10 mmHg) at 24 hours of ECMO support was associated with ABI, particularly CNS ischemia, in peripheral VA-ECMO patients.

Drive in the Moment: An evaluation of a web-based tool designed to reduce smartphone use among young drivers.

OBJECTIVE: Young drivers are overrepresented in road traffic crashes and fatalities. Distracted driving, including use of a smartphone while driving (SWD), is a major risk factor for crashes for this age group. We evaluated a web-based tool (Drive in the Moment or DITM) designed to reduce SWD among young drivers. METHODS: A pretest-posttest experimental design with a follow-up was used to assess the efficacy of the DITM intervention on SWD intentions and behaviors, and perceived risk (of having a crash and of being apprehended by the police) associated with SWD. One hundred and eighty young drivers (aged 17-25 years old) were randomly assigned to either the DITM intervention or a control group where participants completed an unrelated activity. Self-reported measures of SWD and perceptions of risk were obtained pre-intervention, immediately post-intervention and at a follow-up 25 days after the intervention. RESULTS: Participants who engaged with the DITM showed a significant reduction in the number of times they used their SWD at follow-up compared to their pre-intervention scores. Future intentions to SWD were also reduced from pre-intervention to post-intervention and follow-up. There was also an increase in the perceived risk of SWD following the intervention. CONCLUSIONS: Our evaluation of DITM suggests that the intervention had an impact on reducing SWD among young drivers. Further research is needed to establish which particular elements of the DITM are associated with reductions in SWD and whether similar findings would be identified in other age groups.

Body image explains differences in intuitive eating between men and women: Examining indirect effects across negative and positive body image.

Intuitive eating is an adaptive and flexible form of eating. Men report higher rates of intuitive eating than women. Objectification processes are proposed to underlie this (binary) gender difference due to the intense body-related pressures that disrupt body image in women. The current study is the first known to test whether body image indirectly explains lower levels of intuitive eating in women relative to men. A cross-sectional sample of 498 adults aged 18-74 years recruited through Prolific completed an online survey assessing intuitive eating and negative and positive body image indicators. Women reported poorer body image and lower levels of intuitive eating compared to men. Significant indirect effects suggested body image explained gender differences in intuitive eating, controlling for age and body mass index. In women relative to men, greater body surveillance and lower aesthetic satisfaction explained lower total intuitive eating and reliance on hunger and satiety, greater aesthetic investment explained lower total intuitive eating and eating for physical reasons, and lower functionality investment explained lower body-food choice congruence. More research is needed, but findings suggest programs may benefit from decreasing critical views of appearance and strengthening functionality investment in women to reduce gender differences in intuitive eating.

Alternative Splicing of the Flip/Flop Cassette and TARP Auxiliary Subunits Engage in a Privileged Relationship That Fine-Tunes AMPA Receptor Gating.

Alternative splicing of AMPA-type glutamate receptors (AMPARs) and allosteric modulation by auxiliary subunits, such as transmembrane AMPAR regulatory proteins (TARPs), are two important mechanisms that regulate the time course of glutamatergic neurotransmission. Prior work has shown that alternative splicing of the flip/flop cassette profoundly regulates TARP γ2 modulation, where flip receptor gating exhibits robust sensitivity to TARPs while flop isoforms are relatively insensitive to TARP modulation. Whether this splice variant-specific regulation extends to other auxiliary subunit families, such as cornichons (CNIHs), GSG1L, or CKAMPs, remains unknown. Here, we demonstrate that CNIH-3 modulation is unaffected by AMPAR alternative splicing due to inherent differences in how CNIH-3 and TARP γ2 modify channel gating. CNIH-3 slows receptor deactivation from the outset of current decay, consistent with structural evidence showing its point of contact at the level of the pore. In contrast, TARP γ2 acts via the KGK site of the ligand-binding domain (LBD) to slow the onset of desensitization. Although GSG1L and CKAMP44 primarily slow recovery from desensitization, their effects on channel gating are unaffected by alternative splicing, further underlining that structural events leading to the onset and recovery from desensitization are separable. Together, this work establishes that alternative splicing and TARP auxiliary subunits form a unique partnership that governs fast glutamatergic signaling at central synapses. Since proteomic studies suggest that all native AMPARs co-assemble with at least two TARPs, allosteric coupling between the flip/flop cassette and TARPs may represent a common design element in all AMPAR complexes of the mammalian brain.SIGNIFICANCE STATEMENT All fast excitatory neurotransmission in the mammalian brain is mediated by AMPA-type glutamate receptors (AMPARs). The time course of AMPAR gating can be regulated by two distinct mechanisms: alternative splicing of the flip/flop cassette and association with auxiliary subunits. Although these regulatory mechanisms have been well studied individually, it is not clear whether alternative splicing impacts auxiliary protein modulation of AMPARs. Here, we compare the four main families of AMPAR auxiliary subunits, transmembrane AMPAR regulatory proteins (TARPs; γ2), cornichons (CNIH-3), GSG1L and CKAMPs (CKAMP44), and find a privileged relationship between TARPs and the flip/flop cassette that is not shared by others. The flop cassette acts as a master switch to override TARP action, and this coupling represents a way to fine-tune AMPAR signaling.

Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: Analysis of the extracorporeal life support organization registry.

BACKGROUND: Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO2) and carbon dioxide (PaCO2) on ABI occurrence. METHODS: We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO2 and PaCO2 with ABI. RESULTS: Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89). CONCLUSIONS: Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.

Young drivers and smartphone use: The impact of legal and non-legal deterrents.

INTRODUCTION: Young drivers continue to be overrepresented in road crash statistics and smartphone use has been identified as a dangerous form of driver distraction. Previous research has identified factors encouraging drivers to use their mobile phone, with few examining what deters drivers. This study examines the influence of legal and non-legal deterrents on smartphone use while driving (SWD) in a young adult sample. METHOD: An online survey was administered to a sample of 524 Australian drivers aged 17-25 years. Measures included demographic variables, legal deterrents (certainty, severity, and swiftness), and non-legal deterrents: social loss (peers and parents), internal loss (anticipated regret) and physical loss (injury to self/others). Self-reported SWD was the outcome variable, measured separately for initiating SWD and responding SWD behaviors. RESULTS: Responding behaviors were reported more frequently than initiating, and social, internal, and physical loss were perceived as higher for initiating versus responding behaviors. Anticipated action regret and physical loss were significant negative predictors of SWD across both modalities of communication. Anticipated inaction regret was also a significant positive predictor of initiating behaviors. Both legal deterrents and social loss were non-significant predictors for both modalities of SWD. CONCLUSIONS: The results reinforce previous evidence showing that legal deterrence variables are not consistently effective at reducing offending behaviors. Future research should continue to explore the effect of non-legal deterrents across different modalities of SWD. PRACTICAL APPLICATIONS: Road safety interventions aimed at young drivers should evaluate the impact of highlighting anticipated regret and potential injury to self and others associated with risky driving behaviors, such as SWD.