Impairment of Neuronal Activity in the Dorsolateral Prefrontal Cortex Occurs Early in Parkinsonism.

Background: Parkinson's disease (PD) is often characterized by altered rates and patterns of neuronal activity in the sensorimotor regions of the basal ganglia thalamocortical network. Little is known, however, regarding how neuronal activity in the executive control network of the brain changes in the parkinsonian condition. Objective: Investigate the impact of parkinsonism on neuronal activity in the dorsolateral prefrontal cortex (DLPFC), a key region in executive control, during a go/nogo reaching task. Methods: Using a within-subject design, single and multi-unit neuronal activity was recorded in the DLPFC of a nonhuman primate before and after the induction of mild parkinsonism using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Results: Coincident with development of mild parkinsonian motor signs, there was a marked reduction in the percentage of DLPFC cells with significant task-related firing rate modulation during go and nogo conditions. Conclusions: These results suggest that DLPFC dysfunction may occur early in parkinsonism and contribute to cognitive impairments and disrupted executive function often observed in PD patients.

Biomechanical comparison of four isometric prosthetic ligament repair techniques for tarsal medial collateral ligament injury.

OBJECTIVE: To compare the stability, ultimate strength, and isometry of 4 prosthetic ligament repairs for canine tarsal medial collateral ligament injury. METHODS: 24 cadaveric canine distal hind limbs with induced medial tarsal instability were randomly divided into 4 groups. Simulated medial shearing injury of the collateral and medial malleolus were repaired using 1 of 4 isometric suture techniques: bone tunnels with nylon suture (TN), ultrahigh-molecular-weight polyethylene (UHMWPE) suture (TU), tibial bone anchor with nylon suture (AN), or talar bone anchor with UHMWPE suture (AU). Each repair was evaluated for medial stability before and after cyclic range of motion. 3 of 4 repair configurations allowed string potentiometer isometry data collection during cyclic range of motion. Each construct was subsequently tested to failure; the strength and failure mode were recorded. RESULTS: All repair groups showed statistically increased laxity compared to intact ligament. There was no difference in joint laxity between repair techniques. Cyclic range-of-motion testing did not increase joint laxity at any tested joint angle. Strength to failure was no different between repair groups. Isometry was achieved in the TU and TN groups. CONCLUSIONS: All 4 techniques improved medial stability compared to that medial collateral ligament injury; however, no technique returned stability to the tarsal of the intact ligament. All 4 techniques maintained stability after range-of-motion testing. Isometric placement of the prosthetic suture was achievable. The constructs did not provide sufficient resistance to physiologic valgus stress. CLINICAL RELEVANCE: Isometric placement of a prosthetic ligament is possible; secondary stabilization appears necessary to support the repair postoperatively.

A Reduced Resistance, Concentric-Gated Artificial Membrane Lung for Pediatric End-Stage Lung Failure.

The goal of the low-resistance pediatric artificial lung (PAL-LR) is to serve as a pumpless bridge-to-transplant device for children with end-stage lung failure. The PAL-LR doubles the exposed fiber length of the previous PAL design. In vitro and in vivo studies tested hemocompatibility, device flow, gas exchange and pressure drop performance. For in vitro tests, average rated blood flow (outlet SO2 of 95%) was 2.56 ± 0.93 L/min with a pressure drop of 25.88 ± 0.90 mm Hg. At the targeted pediatric flow rate of 1 L/min, the pressure drop was 8.6 mm Hg compared with 25 mm Hg of the PAL. At rated flow, the average O2 and CO2 transfer rates were 101.75 ± 10.81 and 77.93 ± 8.40 mL/min, respectively. The average maximum O2 and CO2 exchange efficiencies were 215.75 ± 22.93 and 176.99 ± 8.40 mL/(min m2), respectively. In vivo tests revealed an average outlet SO2 of 100%, and average pressure drop of 2 ± 0 mm Hg for a blood flow of 1.07 ± 0.02 L/min. Having a lower resistance, the PAL-LR is a promising step closer to a pumpless artificial membrane lung that alleviates right ventricular strain associated with idiopathic pulmonary hypertension.

Family shapes child development: The role of codevelopmental trajectories of interparental conflict and emotional warmth for children's longitudinal development of internalizing and externalizing problems.

This study aimed (1) to identify distinct family trajectory profiles of destructive interparental conflict and parent-child emotional warmth reported by one parent, and (2) to examine whether these codevelopmental profiles were associated with the longitudinal development of children and adolescents' self-reported internalizing and externalizing problems. Six longitudinal data waves from the German Family Panel (pairfam) study (Waves 2-7) from 722 parent-child dyads were used (age of children and adolescents in years: M = 10.03, SD = 1.90, range = 8-15; 48.3% girls; 73.3% of parents were native Germans). Data were analyzed using growth mixture and latent growth curve modeling. Two classes, harmonious and conflictual-warm families, were found based on codevelopmental trajectories of interparental conflict and emotional warmth. These family profiles were linked with the development of externalizing problems in children and adolescents but not their internalizing problems. Family dynamics are entangled in complex ways and constantly changing, which appears relevant to children's behavior problems.

Neural pathways associated with reduced rigidity during pallidal deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity (P < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output.NEW & NOTEWORTHY Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.

Successful Resuscitation of Porcine Hearts After 12 and 24 h of Static Cold Storage With Normothermic Ex Situ Perfusion.

Background: Heart transplantation is always an emergency because the transplant needs to occur within 6 h after procurement to prevent primary graft dysfunction. Static cold storage (SCS) is the gold-standard preservation method. This study describes the outcomes of hearts preserved after prolonged SCS (12 and 24 h); those are then resuscitated with a novel normothermic ex situ heart perfusion (NEHP) system. Methods: Anesthetized piglets (n = 10) were used as heart donors. Hearts were procured and stored at 5 °C CoStorSol following standard SCS protocols. Two groups were studied: SCS-12 h and SCS-24 h. After SCS, 8 h of NEHP (37 °C blood-based perfusate) was performed at 0.7-1.0 mL/min/g of cardiac tissue. NEHP parameters were monitored continuously. Results were corroborated with 3 additional hearts transplanted orthotopically in healthy recipients (n = 3) after SCS (24 h) + NEHP (5 h). Recipients were observed for 90 min after weaning off cardiopulmonary bypass support. Results: All hearts (after 12 and 24 h of SCS) regained normal function and metabolism within 10 min and retained it throughout 8 h of NEHP. No differences were observed in NEHP parameters and histopathology between groups. Three hearts were successfully transplanted after a total ~30 h of preservation (24 h of SCS + 5 h of NEHP + 1 h of second cold ischemia time). The 3 recipients were weaned off cardiopulmonary bypass with mild vasopressor support. Conclusions: NEHP has the potential to routinely resuscitate porcine hearts that have undergone SCS for up to 24 h, restoring them to viable function. By objectively assessing heart function before transplant, NEHP may enhance the success rate of transplants. If these resuscitated hearts can be successfully transplanted, it would support the effectiveness of NEHP in ensuring heart viability.

Spanish-Language Measures of Intimate Partner Violence: A Systematic Review of Psychometric Evidence and Translation Methodology.

Intimate partner violence (IPV) is prevalent worldwide, including in Latinx populations. Reported rates of IPV in Latinx populations vary widely, indicating that measurement errors may be impeding researchers' and clinicians' understanding of IPV in these populations. We conducted a systematic review across a range of social science databases to evaluate psychometric properties and translation methodologies of Spanish-language IPV measures. Records were included if they included Spanish measures assessing IPV victimization. We identified 91 records with a total of 70 measures and evaluated the measures' extant psychometric evidence using the COnsensus-based Standards for the selection of health Measurement Instruments. For the measures translated from English to Spanish, we evaluated the translation methodology based on best-practice recommendations for achieving translations that are psychometrically equivalent to their original versions. We found that validation information about measures was sparse and that few translations adhered to best-practice recommendations. Based on our a priori criteria we recommend the Plazaola-Castaño translation of the Index of Spouse Abuse. In closing, we discuss the validity evidence of translated measures independent of the original language version and best-practice recommendations in translating psychological measures.

Virtual surgical planning and use of a 3D-printed, patient-specific reduction system for minimally invasive plate osteosynthesis of diaphyseal tibial fractures in dogs: A historic case control study.

OBJECTIVE: To compare the efficacy and clinical outcomes of computed tomography (CT)-based virtual surgical planning (VSP) and a three-dimensional (3D)-printed, patient-specific reduction system to conventional indirect reduction techniques for diaphyseal tibial fractures stabilized using minimally invasive plate osteosynthesis (MIPO) in dogs. STUDY DESIGN: A prospective clinical study with a historic control cohort. SAMPLE POPULATION: Dogs undergoing MIPO stabilization of diaphyseal tibial fractures using a custom 3D-printed reduction system (3D-MIPO; n = 15) or conventional indirect reduction techniques (c-MIPO; n = 14). METHODS: Dogs were prospectively enrolled to the 3D-MIPO group and CT scans were used to design and fabricate a custom 3D-printed reduction system to facilitate MIPO. Medical records were searched to identify dogs for the c-MIPO group. Pre-, intra- and postoperative parameters were compared between groups. RESULTS: The duration from presentation until surgery was 23 h longer in the 3D-MIPO group (p = .002). Fewer intraoperative fluoroscopic images were acquired (p < .001) and mean surgical duration was 34 min shorter in the 3D-MIPO group (p = .014). Median postoperative tibial length, frontal alignment, and sagittal alignment were within 4 mm, 3° and 3°, respectively, of the contralateral tibia in both groups and did not differ between reduction groups (p > .1). Postoperative complications occurred in 27% and 14% of fractures in the 3D-MIPO and c-MIPO groups, respectively. CONCLUSION: Both reduction methods yielded comparable results. Although the preoperative planning and guide preparation was time consuming, surgery times were shorter and fluoroscopy use was less in the 3D-MIPO group. CLINICAL SIGNIFICANCE: VSP and the custom 3D-printed reduction system facilitated efficient MIPO.

Large attachment organelle mediates interaction between Nanobdellota archaeon YN1 and its host.

DPANN archaea are an enigmatic superphylum that are difficult to isolate and culture in the laboratory due to their specific culture conditions and apparent ectosymbiotic lifestyle. Here, we successfully isolated and cultivated a coculture system of a novel Nanobdellota archaeon YN1 and its host Sulfurisphaera ohwakuensis YN1HA. We characterized the coculture system by complementary methods, including metagenomics and metabolic pathway analysis, fluorescence microscopy, and high-resolution electron cryo-tomography (cryoET). We show that YN1 is deficient in essential metabolic processes and requires host resources to proliferate. CryoET imaging revealed an enormous attachment organelle present in the YN1 envelope that forms a direct interaction with the host cytoplasm, bridging the two cells. Together, our results unravel the molecular and structural basis of ectosymbiotic relationship between YN1 and YN1HA. This research broadens our understanding of DPANN biology and the versatile nature of their ectosymbiotic relationships.

Cell-to-cell interactions revealed by cryo-tomography of a DPANN co-culture system.

DPANN is a widespread and diverse group of archaea characterized by their small size, reduced genome, limited metabolic pathways, and symbiotic existence. Known DPANN species are predominantly obligate ectosymbionts that depend on their host for proliferation. The structural and molecular details of host recognition, host-DPANN intercellular communication, and host adaptation in response to DPANN attachment remain unknown. Here, we use electron cryotomography (cryo-ET) to show that the Microcaldus variisymbioticus ARM-1 may interact with its host, Metallosphaera javensis AS-7 through intercellular proteinaceous nanotubes. Combining cryo-ET and sub-tomogram averaging, we show the in situ architectures of host and DPANN S-layers and the structures of the nanotubes in their primed and extended states. In addition, comparative proteomics and genomic analyses identified host proteomic changes in response to DPANN attachment. These results provide insights into the structural basis of host-DPANN communication and deepen our understanding of the host ectosymbiotic relationships.

A Reproducible Pipeline for Parcellation of the Anterior Limb of the Internal Capsule.

BACKGROUND: The anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions. METHODS: Following algorithm development and refinement, we analyzed 43 control participants, each with 2 sets of 3T magnetic resonance imaging data and a subset of 5 control participants with 7T data from the Human Connectome Project. We generated 22 segmented ALIC fiber bundles (11 per hemisphere) based on PFC regions of interest, and we analyzed the relationships among bundles. RESULTS: We successfully reproduced the topographies established by previous anatomical work using images acquired at both 3T and 7T. Quantitative assessment demonstrated significantly smaller intraparticipant variability than interparticipant variability for both test and retest groups across all but one PFC region. We examined the overlap between fibers from different PFC regions and a response tract for obsessive-compulsive disorder deep brain stimulation, and we reconstructed the PFC hyperdirect pathway using a modified version of our pipeline. CONCLUSIONS: Our diffusion magnetic resonance imaging algorithm reliably generates biologically validated ALIC white matter reconstructions, thereby allowing for more precise modeling of fibers for neuromodulation therapies.

Efficacy of virtual surgical planning and a three-dimensional-printed, patient-specific reduction system to facilitate alignment of diaphyseal tibial fractures stabilized by minimally invasive plate osteosynthesis in dogs: A prospective clinical study.

OBJECTIVE: To evaluate the efficacy of a three-dimensional (3D)-printed, patient-specific reduction system for aligning diaphyseal tibial fractures stabilized using minimally invasive plate osteosynthesis (MIPO). STUDY DESIGN: Prospective clinical trial. SAMPLE POPULATION: Fifteen client owned dogs. METHODS: Virtual 3D models of both pelvic limbs were created. Pin guides were designed to conform to the proximal and distal tibia. A reduction bridge was designed to align the pin guides based on the guides' spatial location. Guides were 3D printed, sterilized, and applied, in conjunction with transient application of a circular fixator, to facilitate indirect fracture realignment before plate application. Alignment of the stabilized tibiae was assessed using postoperative computed tomography scans. RESULTS: Mean duration required for virtual planning was 2.5 h and a mean of 50.7 h elapsed between presentation and surgery. Guide placement was accurate with minor median discrepancies in translation and frontal, sagittal, and axial plane positioning of 2.9 mm, 3.6°, 2.7°, and 6.8°, respectively. Application of the reduction system restored mean tibial length and frontal, sagittal, and axial alignment within 1.7 mm, 1.9°, 1.7°, and 4.5°, respectively, of the contralateral tibia. CONCLUSION: Design and fabrication of a 3D-printed, patient-specific fracture reduction system is feasible in a relevant clinical timeline. Intraoperative pin-guide placement was reasonably accurate with minor discrepancies compared to the virtual plan. Custom 3D-printed reduction system application facilitated near-anatomic or acceptable fracture reduction in all dogs. CLINICAL SIGNIFICANCE: Virtual planning and fabrication of a 3D-printing patient-specific fracture reduction system is practical and facilitated acceptable, if not near-anatomic, fracture alignment during MIPO.

Pantarsal arthrodesis stabilized with circular external skeletal fixators in 8 dogs (2010-2022).

OBJECTIVE: To report the surgical technique, complications, and outcomes of 8 dogs that underwent a unilateral pantarsal arthrodesis stabilized using a circular external skeletal fixator (CESF) construct for the treatment of uni- or multilevel tarsal instability. ANIMALS: 8 dogs. CLINICAL PRESENTATION: Medical records from 2010 to 2023 from 2 small animal hospitals were retrospectively reviewed for dogs undergoing pantarsal arthrodeses stabilized with CESF. Data collected for each dog included signalment, injury etiology, construct configuration, radiographic imaging, antimicrobial use, complications, length of time until construct removal, and outcome based on clinical evaluation by the owner and veterinary surgeon. RESULTS: 8 dogs met the requirements of inclusion for the study. Dogs had a mean age of 5.5 years (range, 0.42 to 13 years) and weight of 15.1 kg (range, 2.5 to 26.4 kg). Angulated 3- and 4-ring constructs were used in 5 and 3 dogs, respectively, with or without hybridization. Tarsi were stabilized with a mean angle of extension of 124.8° (range, 111.5° to 136.5°). Fixator removal was performed at a mean time of 11.3 weeks (range, 6 to 16 weeks). Complications developed in 4 dogs, 2 of which had poor clinical outcomes despite additional interventions, including recurrent digit trauma and poor limb use postoperatively. Six dogs had excellent outcomes. CLINICAL RELEVANCE: A CESF may be considered as an alternative to plate stabilization when performing a pantarsal arthrodesis. This fixation requires rigorous postoperative care but obviates the need for supplemental postoperative coaptation.

Thank You for Changing: Gratitude Promotes Autonomous Motivation and Successful Partner Regulation.

Romantic partners often attempt to improve their relationship by changing each other's traits and behaviors, but such partner regulation is often unsuccessful. We examined whether gratitude expressed by agents (i.e., partners requesting change) facilitates greater regulation success from targets (i.e., partners making change) by encouraging targets' autonomous motivation. Across studies, including observational (Study 1, N = 111 couples), preregistered longitudinal (Study 2, N = 150 couples), and experimental (Study 3a, N = 431; Study 3b, N = 725) designs, agents' gratitude for targets' efforts was linked to greater targets'-and less consistently agents'-reported regulation success. These effects were consistently mediated by greater target autonomous motivation, and generally persisted when accounting for how agents communicated their change request and other positive responses to targets' efforts (e.g., positivity and support). Gratitude for targets' efforts appears to be an important tool for promoting change success.

Model-based closed-loop control of thalamic deep brain stimulation.

Introduction: Closed-loop control of deep brain stimulation (DBS) is beneficial for effective and automatic treatment of various neurological disorders like Parkinson's disease (PD) and essential tremor (ET). Manual (open-loop) DBS programming solely based on clinical observations relies on neurologists' expertise and patients' experience. Continuous stimulation in open-loop DBS may decrease battery life and cause side effects. On the contrary, a closed-loop DBS system uses a feedback biomarker/signal to track worsening (or improving) of patients' symptoms and offers several advantages compared to the open-loop DBS system. Existing closed-loop DBS control systems do not incorporate physiological mechanisms underlying DBS or symptoms, e.g., how DBS modulates dynamics of synaptic plasticity. Methods: In this work, we propose a computational framework for development of a model-based DBS controller where a neural model can describe the relationship between DBS and neural activity and a polynomial-based approximation can estimate the relationship between neural and behavioral activities. A controller is used in our model in a quasi-real-time manner to find DBS patterns that significantly reduce the worsening of symptoms. By using the proposed computational framework, these DBS patterns can be tested clinically by predicting the effect of DBS before delivering it to the patient. We applied this framework to the problem of finding optimal DBS frequencies for essential tremor given electromyography (EMG) recordings solely. Building on our recent network model of ventral intermediate nuclei (Vim), the main surgical target of the tremor, in response to DBS, we developed neural model simulation in which physiological mechanisms underlying Vim-DBS are linked to symptomatic changes in EMG signals. By using a proportional-integral-derivative (PID) controller, we showed that a closed-loop system can track EMG signals and adjust the stimulation frequency of Vim-DBS so that the power of EMG reaches a desired control target. Results and discussion: We demonstrated that the model-based DBS frequency aligns well with that used in clinical studies. Our model-based closed-loop system is adaptable to different control targets and can potentially be used for different diseases and personalized systems.

Who's doing more and when? Gender, parenting, and housework trajectories.

Drawing on five waves of longitudinal survey data (N = 520, 51% female, 39% with a university degree, 90% White), this study examined trajectories of women's and men's contributions to cooking, kitchen cleaning, grocery shopping, house cleaning, laundry, and overall housework from Age 25 to 50 years and explored time-invariant (traditional gender role attitudes, homemaker mother, mother and father education assessed at Age 18) and time-varying (raising children at Ages 25, 32, 43, and 50 years) predictors of housework trajectories. Growth curve analyses revealed that women contributed more to all housework tasks than men at Age 25, a gender gap maintained to Age 50. Housework increased to Age 32 and stabilized until Age 43 before declining by Age 50 for women's and men's laundry, women's kitchen cleaning, grocery shopping, and overall housework, and men's house cleaning. There was no change in women's and men's trajectory of cooking meals, women's house cleaning, and men's contributions to kitchen cleaning, grocery shopping, and overall housework. Traditional gender role attitudes, having a homemaker mother, and mother's and father's education inconsistently predicted women's and men's trajectories. Raising children, however, was consistently linked with within-person fluctuations in housework. When raising children, women contributed more than average to housework, whereas when men were raising children, they contributed less than normal. The results highlight a gendered pattern of housework evident in the twenties and persisting well into midlife, with parenthood widening the gap. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Distinguishing features of Parkinson's disease fallers based on wireless insole plantar pressure monitoring.

Postural instability is one of the most disabling motor signs of Parkinson's disease (PD) and often underlies an increased likelihood of falling and loss of independence. Current clinical assessments of PD-related postural instability are based on a retropulsion test, which introduces human error and only evaluates reactive balance. There is an unmet need for objective, multi-dimensional assessments of postural instability that directly reflect activities of daily living in which individuals may experience postural instability. In this study, we trained machine-learning models on insole plantar pressure data from 111 participants (44 with PD and 67 controls) as they performed simulated static and active postural tasks of activities that often occur during daily living. Models accurately classified PD from young controls (area under the curve (AUC) 0.99+/- 0.00), PD from age-matched controls (AUC 0.99+/- 0.01), and PD fallers from PD non-fallers (AUC 0.91+/- 0.08). Utilizing features from both static and active postural tasks significantly improved classification performances, and all tasks were useful for separating PD from controls; however, tasks with higher postural threats were preferred for separating PD fallers from PD non-fallers.

A Pumpless Pediatric Artificial Lung Maintains Function for 72 h Without Systemic Anticoagulation Using the Nitric Oxide Surface Anticoagulation System.

BACKGROUND: Children with end-stage lung disease are commonly managed with extracorporeal life support (ECLS) as a bridge to lung transplantation. A pumpless artificial lung (MLung) is a portable alternative to ECLS and it allows for ambulation. Both ECLS and pumpless artificial lungs require systemic anticoagulation which is associated with hemorrhagic complications. We tested the MLung with a novel Nitric Oxide (NO) Surface Anticoagulation (NOSA) system, to provide local anticoagulation for 72 h of support in a pediatric-size ovine model. METHODS: Four mini sheep underwent thoracotomy and cannulation of the pulmonary artery (inflow) and left atrium (outflow), recovered and were monitored for 72hr. The circuit tubing and connectors were coated with the combination of an NO donor (diazeniumdiolated dibutylhexanediamine; DBHD-N2O2) and argatroban. The animals were connected to the MLung and 100 ppm of NO was added to the sweep gas. Systemic hemodynamics, blood chemistry, blood gases, and methemoglobin were collected. RESULTS: Mean device flow was 836 ± 121 mL/min. Device outlet saturation was 97 ± 4%. Pressure drop across the lung was 3.5 ± 1.5 mmHg and resistance was 4.3 ± 1.7 mmHg/L/min. Activated clotting time averaged 170 ± 45s. Methemoglobin was 2.9 ± 0.8%. Platelets declined from 590 ± 101 at baseline to 160 ± 90 at 72 h. NO flux (x10-10 mol/min/cm2) of the NOSA circuit averaged 2.8 ± 0.6 (before study) and 1.9 ± 0.1 (72 h) and across the MLung 18 ± 3 NO flux was delivered. CONCLUSION: The MLung is a more portable form of ECLS that demonstrates effective gas exchange for 72 h without hemodynamic changes. Additionally, the NOSA system successfully maintained local anticoagulation without evidence of systemic effects.

Extracorporeal life support without systemic anticoagulation: a nitric oxide-based non-thrombogenic circuit for the artificial placenta in an ovine model.

BACKGROUND: Clinical translation of the extracorporeal artificial placenta (AP) is impeded by the high risk for intracranial hemorrhage in extremely premature newborns. The Nitric Oxide Surface Anticoagulation (NOSA) system is a novel non-thrombogenic extracorporeal circuit. This study aims to test the NOSA system in the AP without systemic anticoagulation. METHODS: Ten extremely premature lambs were delivered and connected to the AP. For the NOSA group, the circuit was coated with DBHD-N2O2/argatroban, 100 ppm nitric oxide was blended into the sweep gas, and no systemic anticoagulation was given. For the Heparin control group, a non-coated circuit was used and systemic anticoagulation was administered. RESULTS: Animals survived 6.8 ± 0.6 days with normal hemodynamics and gas exchange. Neither group had any hemorrhagic or thrombotic complications. ACT (194 ± 53 vs. 261 ± 86 s; p < 0.001) and aPTT (39 ± 7 vs. 69 ± 23 s; p < 0.001) were significantly lower in the NOSA group than the Heparin group. Platelet and leukocyte activation did not differ significantly from baseline in the NOSA group. Methemoglobin was 3.2 ± 1.1% in the NOSA group compared to 1.6 ± 0.6% in the Heparin group (p < 0.001). CONCLUSIONS: The AP with the NOSA system successfully supported extremely premature lambs for 7 days without significant bleeding or thrombosis. IMPACT: The Nitric Oxide Surface Anticoagulation (NOSA) system provides effective circuit-based anticoagulation in a fetal sheep model of the extracorporeal artificial placenta (AP) for 7 days. The NOSA system is the first non-thrombogenic circuit to consistently obviate the need for systemic anticoagulation in an extracorporeal circuit for up to 7 days. The NOSA system may allow the AP to be implemented clinically without systemic anticoagulation, thus greatly reducing the intracranial hemorrhage risk for extremely low gestational age newborns. The NOSA system could potentially be applied to any form of extracorporeal life support to reduce or avoid systemic anticoagulation.

Environment-dependent metabolic investments in the mixotrophic chrysophyte Ochromonas.

Mixotrophic protists combine photosynthesis and phagotrophy to obtain energy and nutrients. Because mixotrophs can act as either primary producers or consumers, they have a complex role in marine food webs and biogeochemical cycles. Many mixotrophs are also phenotypically plastic and can adjust their metabolic investments in response to resource availability. Thus, a single species's ecological role may vary with environmental conditions. Here, we quantified how light and food availability impacted the growth rates, energy acquisition rates, and metabolic investment strategies of eight strains of the mixotrophic chrysophyte, Ochromonas. All eight Ochromonas strains photoacclimated by decreasing chlorophyll content as light intensity increased. Some strains were obligate phototrophs that required light for growth, while other strains showed stronger metabolic responses to prey availability. When prey availability was high, all eight strains exhibited accelerated growth rates and decreased their investments in both photosynthesis and phagotrophy. Photosynthesis and phagotrophy generally produced additive benefits: In low-prey environments, Ochromonas growth rates increased to maximum, light-saturated rates with increasing light but increased further with the addition of abundant bacterial prey. The additive benefits observed between photosynthesis and phagotrophy in Ochromonas suggest that the two metabolic modes provide nonsubstitutable resources, which may explain why a tradeoff between phagotrophic and phototrophic investments emerged in some but not all strains.