Anticoagulation Can Be Held in Traumatically Injured Patients on Veno-Venous Extracorporeal Membrane Oxygenation Support.

Traumatic injury is associated with several pulmonary complications, including pulmonary contusion, transfusion-related acute lung injury (TRALI), and the development of acute respiratory distress syndrome (ARDS). There is a lack of literature on these patients supported with veno-venous extracorporeal oxygenation (VV ECMO). Understanding the safety of using VV ECMO to support trauma patients and the ability to hold anticoagulation is important to broaden utilization. This is a single-center retrospective cohort study of adult trauma patients cannulated for VV ECMO during their initial admission over an 8 year period (2014-2021). We hypothesize that anticoagulation can be held in trauma patients on VV ECMO without increasing mortality or prothrombotic complications. We also describe the coagulopathy of traumatically injured patients on VV ECMO. Withholding anticoagulation was not associated with mortality in our study population, and there were no significant differences in bleeding or clotting complications between patients who did and did not receive systemic anticoagulation. Patients in the nonsurvivor group had increased coagulopathy both pre- and post-cannulation. Our study suggests anticoagulation can be safely withheld in traumatically injured VV ECMO patients without increasing mortality, complication rates, or transfusion requirements. Future, multicenter prospective studies with larger sample sizes are required to confirm our results.

Foraging Under Uncertainty Follows the Marginal Value Theorem with Bayesian Updating of Environment Representations.

Foraging theory has been a remarkably successful approach to understanding the behavior of animals in many contexts. In patch-based foraging contexts, the marginal value theorem (MVT) shows that the optimal strategy is to leave a patch when the marginal rate of return declines to the average for the environment. However, the MVT is only valid in deterministic environments whose statistics are known to the forager; naturalistic environments seldom meet these strict requirements. As a result, the strategies used by foragers in naturalistic environments must be empirically investigated. We developed a novel behavioral task and a corresponding computational framework for studying patch-leaving decisions in head-fixed and freely moving mice. We varied between-patch travel time, as well as within-patch reward depletion rate, both deterministically and stochastically. We found that mice adopt patch residence times in a manner consistent with the MVT and not explainable by simple ethologically motivated heuristic strategies. Critically, behavior was best accounted for by a modified form of the MVT wherein environment representations were updated based on local variations in reward timing, captured by a Bayesian estimator and dynamic prior. Thus, we show that mice can strategically attend to, learn from, and exploit task structure on multiple timescales simultaneously, thereby efficiently foraging in volatile environments. The results provide a foundation for applying the systems neuroscience toolkit in freely moving and head-fixed mice to understand the neural basis of foraging under uncertainty.

Electrochemical fluorescence switching of enhanced green fluorescent protein.

Switchable fluorescent proteins, for which fluorescence can be switched ON and OFF, are widely used for molecule tracking and super resolution imaging. However, the robust use of the switchable fluorescent proteins is still limited as either the switching is not repeatable, or such switching requires irradiation with coupled lasers of different wavelengths. Herein, we report an electrochemical approach to reversible fluorescence switching for enhanced green fluorescent proteins (EGFP) on indium tin oxide coated glass. Our results demonstrate that negative and positive electrochemical potentials can efficiently switch the fluorescent proteins between the dim (OFF) and bright (ON) states at the single molecule level. The electrochemical fluorescence switching is fast, reversible, and may be performed up to hundreds of cycles before photobleaching occurs. These findings highlight that this method of electrochemical fluorescence switching can be incorporated into advanced fluorescence microscopy.

Microscopic-scale magnetic recording of brain neuronal electrical activity using a diamond quantum sensor.

Quantum sensors using solid state qubits have demonstrated outstanding sensitivity, beyond that possible using classical devices. In particular, those based on colour centres in diamond have demonstrated high sensitivity to magnetic field through exploiting the field-dependent emission of fluorescence under coherent control using microwaves. Given the highly biocompatible nature of diamond, sensing from biological samples is a key interdisciplinary application. In particular, the microscopic-scale study of living systems can be possible through recording of temperature and biomagnetic field. In this work, we use such a quantum sensor to demonstrate such microscopic-scale recording of electrical activity from neurons in fragile living brain tissue. By recording weak magnetic field induced by ionic currents in mouse corpus callosum axons, we accurately recover signals from neuronal action potential propagation while demonstrating in situ pharmacology. Our sensor allows recording of the electrical activity in neural circuits, disruption of which can shed light on the mechanisms of disease emergence. Unlike existing techniques for recording activity, which can require potentially damaging direct interaction, our sensing is entirely passive and remote from the sample. Our results open a promising new avenue for the microscopic recording of neuronal signals, offering the eventual prospect of microscopic imaging of electrical activity in the living mammalian brain.

Early veno-venous extracorporeal membrane oxygenation is an effective strategy for traumatically injured patients presenting with refractory respiratory failure.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) is used for respiratory failure when standard therapy fails. Optimal trauma care requires patients be stable enough to undergo procedures. Early VV ECMO (EVV) to stabilize trauma patients with respiratory failure as part of resuscitation could facilitate additional care. As VV ECMO technology is portable and prehospital cannulation possible, it could also be used in austere environments. We hypothesize that EVV facilitates injury care without worsening survival. METHODS: Our single center, retrospective cohort study included all trauma patients between January 1, 2014, and August 1, 2022, who were placed on VV ECMO. Early VV was defined as cannulation ≤48 hours from arrival with subsequent operation for injuries. Data were analyzed with descriptive statistics. Parametric or nonparametric statistics were used based on the nature of the data. After testing for normality, significance was defined as a p < 0.05. Logistic regression diagnostics were performed. RESULTS: Seventy-five patients were identified and 57 (76%) underwent EVV. There was no difference in survival between the EVV and non-EVV groups (70% vs. 61%, p = 0.47). Age, race, and gender did not differ between EVV survivors and nonsurvivors. Time to cannulation (4.5 hours vs. 8 hours, p = 0.39) and injury severity scores (34 vs. 29, p = 0.74) were similar. Early VV survivors had lower lactic acid levels precannulation (3.9 mmol/L vs. 11.9 mmol/L, p < 0.001). A multivariable logistic regression analysis examining admission and precannulation laboratory and hemodynamic values demonstrated that lower precannulation lactic acid levels predicted survival (odds ratio, 1.2; 95% confidence interval, 1.02-1.5; p = 0.03), with a significant inflection point of 7.4 mmol/L corresponding to decreased survival at hospital discharge. CONCLUSION: Patients undergoing EVV did not have increased mortality compared with the overall trauma VV ECMO population. Early VV resulted in ventilatory stabilization that allowed subsequent procedural treatment of injuries. LEVEL OF EVIDENCE: Therapeutic Care/Management; Level III.

Atypical symptom reporting after mild traumatic brain injury.

OBJECTIVE: Early reporting of atypical symptoms following a mild traumatic brain injury (mTBI) may be an early indicator of poor prognosis. This study aimed to determine the percentage of people reporting atypical symptoms 1-month post-mTBI and explore links to recovery 12 months later in a community-dwelling mTBI sample. METHODS: Adult participants (>16 years) who had experienced a mTBI were identified from a longitudinal incidence study (BIONIC). At 1-month post-injury, 260 participants completed the Rivermead Post-Concussion Symptoms Questionnaire (typical symptoms) plus four atypical symptom items (hemiplegia, difficulty swallowing, digestion problems and difficulties with fine motor tasks). At 12 months post-injury, 73.9% (n = 193) rated their overall recovery on a 100-point scale. An ordinal regression explored the association between atypical symptoms at 1 month and recovery at 12 months post-injury (low = 0-80, moderate = 81-99 and complete recovery = 100), whilst controlling for age, sex, rehabilitation received, ethnicity, mental and physical comorbidities and additional injuries sustained at the time of injury. RESULTS: At 1-month post-injury <1% of participants reported hemiplegia, 5.4% difficulty swallowing, 10% digestion problems and 15.4% difficulties with fine motor tasks. The ordinal regression model revealed atypical symptoms were not significant predictors of self-rated recovery at 12 months. Older age at injury and higher typical symptoms at 1 month were independently associated with poorer recovery at 12 months, p < 0.01. CONCLUSION: Atypical symptoms on initial presentation were not linked to global self-reported recovery at 12 months. Age at injury and typical symptoms are stronger early indicators of longer-term prognosis. Further research is needed to determine if atypical symptoms predict other outcomes following mTBI.

An adhesive and resilient hydrogel for the sealing and treatment of gastric perforation.

Adhesive hydrogels have been recently proposed as a potential option to seal and treat gastric perforation (GP) which causes high mortality despite advancements in surgical treatments. However, to be effective, the hydrogels must have sufficient tissue adhesiveness, tough mechanical property, tunable biodegradability and ideally are easy to apply and form. Herein, we report an adhesive and resilient hydrogel for the sealing and treatment of gastric perforation. The hydrogel consists of a bioactive, transglutaminase (TG)-crosslinked gelatin network and a dynamic, borate-crosslinked poly-N-[Tris(hydroxymethyl)methyl]acrylamide (PTH) network. The hydrogel can be formed in situ, facilitating easy delivery to the GP and allowing for precise sealing of the defects. In vivo experiments, using a perforated stomach mouse model, shows that the adhesive hydrogel plug effectively seals GP defects and promotes gastric mucosa regeneration. Overall, this hydrogel represents a promising biomaterial for GP treatment.

Syndemic anemia in British Malaya: An early global health encounter with hookworm and malaria co-infections in plantation workers.

With the establishment of the International Health Commission in 1913, the Rockefeller Foundation sought governmental partnerships overseas to combat hookworm disease and improve feces disposal practices. In the Madras Presidency in British India, the India Research Fund Association carried out hookworm surveys but failed in its educational efforts to improve feces disposal practices. In British Malaya, the Uncinariasis [Hookworm] Commission to the Orient discovered a syndemic of anemia among Tamil plantation laborers from the Madras Presidency and Chinese laborers from southern China who suffered from hookworm and malarial co-infections. Confronted with the apparent infeasibility of improving feces disposal practices and the obdurate fact of re-infection with hookworm after purgative treatment, the Rockefeller Foundation ended its hookworm initiative in British Malaya without advocating for programmatic intervention against syndemic anemia. The essay concludes with a reflection on the engagement of historians with the syndemic paradigm.

Feasibility of administering the WAIS-IV using a home-based telehealth videoconferencing model.

Use of telehealth to deliver neuropsychological services has proven to be a feasible approach, however, there is limited research which has examined the reliability of home-based assessment models using a comprehensive intelligence test. The aim of this study was to examine the reliability and feasibility of a home-based videoconferencing administration of the Wechsler Adult Intelligence Scales-4th Edition (WAIS-IV).Thirty healthy participants (aged 18-40 years) completed the WAIS-IV both in-person and via home-based videoconferencing utilizing a randomized counter-balanced methodology to attempt to control for an order effect. Paper record forms for Coding/Symbol Search and Blocks were sent and returned via tamper proof courier packs. Participants completed an online survey of their experiences of TNP following completion of their assessments. Group mean comparisons, intra class correlation coefficients (ICCs) and Bland-Altman measures of bias were calculated.Findings from both modalities were highly concordant across all WAIS-IV subtests and indices, with all ICCs rated as "excellent," (≥0.9). There were no significant mean group differences and no evidence of proportional bias. The majority of participants were very satisfied with the use of videoconferencing as an application for cognitive assessment and high levels of participant compliance were observed.In this non-clinical cohort home-based videoconference administration of the WAIS-IV was feasible, reliable and acceptable. TNP may offer an alternative for those consumers where there are challenges in accessing a face-to-face service delivery model, thereby improving equity, and enabling continuation of service delivery. Future research is needed with a larger and more ethnically diverse clinical population.

STEMI Mimic: Focal Myocarditis in an Adolescent Patient After mRNA COVID-19 Vaccine.

BACKGROUND: In May 2021, the U.S. Food and Drug Administration expanded the Emergency Use Authorization for the Pfizer-BioNTech mRNA Coronavirus disease 2019 (COVID-19) Vaccine (BNT162b2) to include adolescents 12-15 years of age. As vaccine administration continues to increase, potential adverse outcomes, to include myocarditis, are being reported to the Vaccine Adverse Event Reporting System. CASE REPORT: This case report describes a 17-year-old male patient who developed focal myocarditis mimicking an ST-segment elevation myocardial infarction (STEMI) 3 days after administration of an mRNA COVID-19 vaccine. Why Should an Emergency Physician Be Aware of This? Myocarditis is a rare complication in adolescents receiving mRNA COVID-19 vaccines. Focal myocarditis may demonstrate localizing electrocardiographic changes consistent with a STEMI. Overall, complications of the mRNA COVID-19 vaccines are extremely rare. The vaccine continues to be recommended by public health experts, as the benefits of vaccinations greatly outweigh the rare side effects.

In-vitro Recordings of Neural Magnetic Activity From the Auditory Brainstem Using Color Centers in Diamond: A Simulation Study.

Magnetometry based on nitrogen-vacancy (NV) centers in diamond is a novel technique capable of measuring magnetic fields with high sensitivity and high spatial resolution. With the further advancements of these sensors, they may open up novel approaches for the 2D imaging of neural signals in vitro. In the present study, we investigate the feasibility of NV-based imaging by numerically simulating the magnetic signal from the auditory pathway of a rodent brainstem slice (ventral cochlear nucleus, VCN, to the medial trapezoid body, MNTB) as stimulated by both electric and optic stimulation. The resulting signal from these two stimulation methods are evaluated and compared. A realistic pathway model was created based on published data of the neural morphologies and channel dynamics of the globular bushy cells in the VCN and their axonal projections to the principal cells in the MNTB. The pathway dynamics in response to optic and electric stimulation and the emitted magnetic fields were estimated using the cable equation. For simulating the optic stimulation, the light distribution in brain tissue was numerically estimated and used to model the optogenetic neural excitation based on a four state channelrhodopsin-2 (ChR2) model. The corresponding heating was also estimated, using the bio-heat equation and was found to be low (<2°C) even at excessively strong optic signals. A peak magnetic field strength of ∼0.5 and ∼0.1 nT was calculated from the auditory brainstem pathway after electrical and optical stimulation, respectively. By increasing the stimulating light intensity four-fold (far exceeding commonly used intensities) the peak magnetic signal strength only increased to 0.2 nT. Thus, while optogenetic stimulation would be favorable to avoid artefacts in the recordings, electric stimulation achieves higher peak fields. The present simulation study predicts that high-resolution magnetic imaging of the action potentials traveling along the auditory brainstem pathway will only be possible for next generation NV sensors. However, the existing sensors already have sufficient sensitivity to support the magnetic sensing of cumulated neural signals sampled from larger parts of the pathway, which might be a promising intermediate step toward further maturing this novel technology.

Detection of biological signals from a live mammalian muscle using an early stage diamond quantum sensor.

The ability to perform noninvasive and non-contact measurements of electric signals produced by action potentials is essential in biomedicine. A key method to do this is to remotely sense signals by the magnetic field they induce. Existing methods for magnetic field sensing of mammalian tissue, used in techniques such as magnetoencephalography of the brain, require cryogenically cooled superconducting detectors. These have many disadvantages in terms of high cost, flexibility and limited portability as well as poor spatial and temporal resolution. In this work we demonstrate an alternative technique for detecting magnetic fields generated by the current from action potentials in living tissue using nitrogen vacancy centres in diamond. With 50 pT/[Formula: see text] sensitivity, we show the first measurements of magnetic sensing from mammalian tissue with a diamond sensor using mouse muscle optogenetically activated with blue light. We show these proof of principle measurements can be performed in an ordinary, unshielded lab environment and that the signal can be easily recovered by digital signal processing techniques. Although as yet uncompetitive with probe electrophysiology in terms of sensitivity, we demonstrate the feasibility of sensing action potentials via magnetic field in mammals using a diamond quantum sensor, as a step towards microscopic imaging of electrical activity in a biological sample using nitrogen vacancy centres in diamond.

Pollen-inspired enzymatic microparticles to reduce organophosphate toxicity in managed pollinators.

Pollinators support the production of the leading food crops worldwide. Organophosphates are a heavily used group of insecticides that pollinators can be exposed to, especially during crop pollination. Exposure to lethal or sublethal doses can impair fitness of wild and managed bees, risking pollination quality and food security. Here we report a low-cost, scalable in vivo detoxification strategy for organophosphate insecticides involving encapsulation of phosphotriesterase (OPT) in pollen-inspired microparticles (PIMs). We developed uniform and consumable PIMs capable of loading OPT at 90% efficiency and protecting OPT from degradation in the pH of a bee gut. Microcolonies of Bombus impatiens fed malathion-contaminated pollen patties demonstrated 100% survival when fed OPT-PIMs but 0% survival with OPT alone, or with plain sucrose within five and four days, respectively. Thus, the detrimental effects of malathion were eliminated when bees consumed OPT-PIMs. This design presents a versatile treatment that can be integrated into supplemental feeds such as pollen patties or dietary syrup for managed pollinators to reduce risk of organophosphate insecticides.

Novel Virtual Reality System for Auditory Tasks in Head-fixed Mice.

An emerging corpus of research seeks to use virtual realities (VRs) to understand the neural mechanisms underlying spatial navigation and decision making in rodents. These studies have primarily used visual stimuli to represent the virtual world. However, auditory cues play an important role in navigation for animals, especially when the visual system cannot detect objects or predators. We have developed a virtual reality environment defined exclusively by free-field acoustic landmarks for head-fixed mice. We trained animals to run in a virtual environment with 3 acoustic landmarks. We present evidence that they can learn to navigate in our context: we observed anticipatory licking and modest anticipatory slowing preceding the reward region. Furthermore, we found that animals were highly aware of changes in landmark cues: licking behavior changed dramatically when the familiar virtual environment was switched to a novel one, and then rapidly reverted to normal when the familiar virtual environment was re-introduced, all within the same session. Finally, while animals executed the task, we performed in-vivo calcium imaging in the CA1 region of the hippocampus using a modified Miniscope.org system. Our experiments point to a future in which auditory virtual reality can be used to expand our understanding of the neural bases of audition in locomoting animals and the variety of sensory cues which anchor spatial representations in a new virtual environment.

HEART Score of Four for Age and Risk Factors: A Case Series.

Chest pain is a frequent chief complaint in the ED. Identifying acute coronary syndrome (ACS) and establishing proper disposition for further risk assessment for major adverse cardiac events are paramount. The HEART Score is a key decision-making tool used to determine patient risk and disposition. One scenario with a potential drawback of the HEART Score is found in patients with a score of four based solely on age and risk factors. The HEART Score categorizes a score of three or less as low risk, and patients with scores above this threshold are typically admitted. We present six cases of chest pain presenting to a military emergency department with a score of four based solely on age and risk factors. They represent every such case found in a previously created database used to validate the HEART Score. We followed each case forward one year in electronic medical records to identify major adverse cardiac events. With the exception of one case that was placed on hospice for non-cardiac reasons and subsequently lost to follow up, there were no adverse events. There is a rising concern for increasing hospital admission rates, overuse of resources, and cost. We highlight that this subset of HEART Score patients requires a more nuanced risk stratification in the ED. It may be worth the time and effort to risk stratify this subset with coronary computed tomography angiography. This additional effort may help reduce admission at such a patient's current and future presentations to the ED for chest pain.

An Adhesive Hydrogel with "Load-Sharing" Effect as Tissue Bandages for Drug and Cell Delivery.

Hydrogels with adhesive properties have potential for numerous biomedical applications. Here, the design of a novel, intrinsically adhesive hydrogel and its use in developing internal therapeutic bandages is reported. The design involves incorporation of "triple hydrogen bonding clusters" (THBCs) as side groups into the hydrogel matrix. The THBC through a unique "load sharing" effect and an increase in bond density results in strong adhesions of the hydrogel to a range of surfaces, including glass, plastic, wood, poly(tetrafluoroethylene) (PTFE), stainless steel, and biological tissues, even without any chemical reaction. Using the adhesive hydrogel, tissue-adhesive bandages are developed for either targeted and sustained release of chemotherapeutic nanodrug for liver cancer treatment, or anchored delivery of pancreatic islets for a potential type 1 diabetes (T1D) cell replacement therapy. Stable adhesion of the bandage inside the body enables almost complete tumor suppression in an orthotopic liver cancer mouse model and ≈1 month diabetes correction in chemically induced diabetic mice.

Historical epidemiology and global health history.

The subdiscipline of historical epidemiology holds the promise of creating a more robust and more nuanced foundation for global public health decision-making by deepening the empirical record from which we draw lessons about past interventions. This essay draws upon historical epidemiological research on three global public health campaigns to illustrate this promise: the Rockefeller Foundation's efforts to control hookworm disease (1909-c.1930), the World Health Organization's pilot projects for malaria eradication in tropical Africa (1950s-1960s), and the international efforts to shut down the transmission of Ebola virus disease during outbreaks in tropical Africa (1974-2019).

Operando Surface Characterization of InP Nanowire p-n Junctions.

We present an in-depth analysis of the surface band alignment and local potential distribution of InP nanowires containing a p-n junction using scanning probe and photoelectron microscopy techniques. The depletion region is localized to a 15 nm thin surface region by scanning tunneling spectroscopy and an electronic shift of up to 0.5 eV between the n- and p-doped nanowire segments was observed and confirmed by Kelvin probe force microscopy. Scanning photoelectron microscopy then allowed us to measure the intrinsic chemical shift of the In 3d, In 4d, and P 2p core level spectra along the nanowire and the effect of operating the nanowire diode in forward and reverse bias on these shifts. Thanks to the high-resolution techniques utilized, we observe fluctuations in the potential and chemical energy of the surface along the nanowire in great detail, exposing the sensitive nature of nanodevices to small scale structural variations.

Observing the Reversible Single Molecule Electrochemistry of Alexa Fluor 647 Dyes by Total Internal Reflection Fluorescence Microscopy.

Alexa Fluor 647 is a widely used fluorescent probe for cell bioimaging and super-resolution microscopy. Herein, the reversible fluorescence switching of Alexa Fluor 647 conjugated to bovine serum albumin (BSA) and adsorbed onto indium tin oxide (ITO) electrodes under electrochemical potential control at the level of single protein molecules is reported. The modulation of the fluorescence as a function of potential was observed using total internal reflectance fluorescence (TIRF) microscopy. The fluorescence intensity of the Alexa Fluor 647 decreased, or reached background levels, at reducing potentials but returned to normal levels at oxidizing potentials. These electrochemically induced changes in fluorescence were sensitive to pH despite that BSA-Alexa Fluor 647 fluorescence without applied potential is insensitive to pH between values of 4-10. The observed pH dependence indicated the involvement of electron and proton transfer in the fluorescence switching mechanism.