Evaluating diverse electrode surface patterns of 3D printed carbon thermoplastic electrochemical sensors.

Electrochemical sensing techniques rely on redox reactions taking place at the electrode surface. The configuration of this surface is of the utmost importance in the advancement of electrochemical sensors. The majority of previous electrode manufacturing methods, including 3D printing have produced electrodes with flat surfaces. There is a distinct potential for 3D printing to create intricate and distinctive electrode surface shapes. In the proposed work, 3D printed carbon black polylactic acid electrodes with nine different surface morphologies were made. These were compared to a flat surface electrode. To evaluate the performance of the electrodes, measurements were conducted in three different redox probes (ferrocene methanol, ferricyanide, and dopamine). Our findings highlighted that when electrodes were normalised for the geometric surface area of the electrode, the surface pattern of the electrode surface can impact the observed current and electron transfer kinetics. Electrodes that had a dome and flag pattern on the electrode surface showed the highest oxidation currents and had lower values for the difference between the anodic and cathodic peak current (ΔE). However, designs with rings had lower current values and higher ΔE values. These differences are most likely due to variations in the accessibility of conductive sites on the electrode surface due to the varying surface roughness of different patterned designs. Our findings highlight that when making electrodes using 3D printing, surface patterning of the electrode surface can be used as an effective approach to enhance the performance of the sensor for varying applications.

Factors affecting dialysis duration in children with Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome.

BACKGROUND: Predicting disease severity can be informative for management of HUS. Dialysis requirement, volume depletion, elevated white blood cell counts, very young age, and use of antimotility agents are known factors associated with severe HUS. METHODS: A retrospective cohort analysis was performed to identify factors associated with dialysis duration using electronic medical record and chart review of 76 children ≤ 18 years of age at presentation with STEC-HUS identified through billing data from July 2008 to April 2020 at James Whitcomb Riley Hospital for Children, Indiana University, Indiana. RESULTS: Novel findings associated with prolonged dialysis duration were age ≥ 6 years old at presentation (p = 0.041) and lack of drop in platelets below 60,000/mm3 anytime during the illness (p = 0.015). In addition, children with NSAID exposure trended longer on dialysis: 15 days with vs. 10 days without (p = 0.117). Known risk factors for severe disease including elevated peak white blood cell (WBC) count and higher hematocrit at presentation were also associated with longer dialysis duration: children with peak WBC > 20,000/mm3 were on dialysis for 15 vs. 9.5 days (p = 0.002) and in children on dialysis ≥ 14 days hematocrit at presentation was 29.6% vs. 24.2% (p = 0.03). Children requiring dialysis for 20 days or longer were more likely to be on anti-hypertensive medications (p = 0.025) and have chronic kidney disease at 12-month follow up (p = 0.044). CONCLUSIONS: Age ≥ 6, elevated WBC count > 20,000/mm3, higher hematocrit at presentation, lack of drop in platelets to < 60,000/mm3, and possibly NSAID exposure during illness are associated with longer dialysis duration in STEC-HUS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Mn(III) Porphyrin, MnTnBuOE-2-PyP5+, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress.

Myocardial ischemia-reperfusion injury (I/R) causes damage to cardiomyocytes through oxidative stress and apoptosis. We investigated the cardioprotective effects of MnTnBuOE-2-PyP5+ (BMX-001), a superoxide dismutase mimic, in an in vitro model of I/R injury in H9c2 cardiomyocytes. We found that BMX-001 protected against hypoxia/reoxygenation (H/R)-induced oxidative stress, as evident by a significant reduction in intracellular and mitochondrial superoxide levels. BMX-001 pre-treatment also reduced H/R-induced cardiomyocyte apoptosis, as marked by a reduction in TUNEL-positive cells. We further demonstrated that BMX-001 pre-treatment significantly improved mitochondrial function, particularly O2 consumption, in mouse adult cardiomyocytes subjected to H/R. BMX-001 treatment also attenuated cardiolipin peroxidation, 4-hydroxynonenal (4-HNE) level, and 4-HNE adducted proteins following H/R injury. Finally, the pre-treatment with BMX-001 improved cell viability and lactate dehydrogenase (LDH) activity in H9c2 cells following H/R injury. Our findings suggest that BMX-001 has therapeutic potential as a cardioprotective agent against oxidative stress-induced H/R damage in H9c2 cardiomyocytes.

Monitoring the electroactive cargo of extracellular vesicles can differentiate various cancer cell lines.

Extracellular vesicles (EVs) are pivotal in cell-to-cell communication due to the array of cargo contained within these vesicles. EVs are considered important biomarkers for identification of disease, however most measurement approaches have focused on monitoring specific surface macromolecular targets. Our study focuses on exploring the electroactive component present within cargo from EVs obtained from various cancer and non-cancer cell lines using a disk carbon fiber microelectrode. Variations in the presence of oxidizable components were observed when the total cargo from EVs were measured, with the highest current detected in EVs from MCF7 cells. There were differences observed in the types of oxidizable species present within EVs from MCF7 and A549 cells. Single entity measurements showed clear spikes due to the detection of oxidizable cargo within EVs from MCF7 and A549 cells. These studies highlight the promise of monitoring EVs through the presence of varying electroactive components within the cargo and can drive a wave of new strategies towards specific detection of EVs for diagnosis and prognosis of various diseases.

Influence of instrument parameters on the electrochemical activity of 3D printed carbon thermoplastic electrodes.

3D printing provides a reliable approach for the manufacture of carbon thermoplastic composite electrochemical sensors. Many studies have explored the impact of printing parameters on the electrochemical activity of carbon thermoplastic electrodes but limited is known about the influence of instrument parameters, which have been shown to alter the structure and mechanical strength of 3D printed thermoplastics. We explored the impact of extruder temperature, nozzle diameter and heated bed temperature on the electrochemical activity of carbon black/poly-lactic acid (CB/PLA) electrodes. Cyclic voltammetry and electrochemical impedance spectroscopy measurements were conducted using standard redox probes. The electrode surface and cross-section of the electrode was visualised using scanning electron microscopy. We found that using extruder temperatures of 230 °C and 240 °C improved the electrochemical activity of CB/PLA electrodes, due to an increase in surface roughness and a reduction in the number of voids in-between print layers. Nozzle diameter, heated bed temperature of different 3D printers did not impact the electrochemical activity of CB/PLA electrodes. However high-end printers provide improved batch reproducibility of electrodes. These findings highlight the key instrument parameters that need to be considered when manufacturing carbon thermoplastic composite electrochemical sensors when using 3D printing.

Endothelial Specific Deletion of Autotaxin Improves Stroke Outcomes.

Autotaxin (ATX) is an extracellular secretory enzyme (lysophospholipase D) that catalyzes the hydrolysis of lysophosphatidyl choline to lysophosphatidic acid (LPA). The ATX-LPA axis is a well-known pathological mediator of liver fibrosis, metastasis in cancer, pulmonary fibrosis, atherosclerosis, and neurodegenerative diseases. Additionally, it is believed that LPA may cause vascular permeability. In ischemic stroke, vascular permeability leading to hemorrhagic transformation is a major limitation for therapies and an obstacle to stroke management. Therefore, in this study, we generated an endothelial-specific ATX deletion in mice (ERT2 ATX-/-) to observe stroke outcomes in a mouse stroke model to analyze the role of endothelial ATX. The AR2 probe and Evans Blue staining were used to perform the ATX activity and vascular permeability assays, respectively. Laser speckle imaging was used to observe the cerebral blood flow following stroke. In this study, we observed that stroke outcomes were alleviated with the endothelial deletion of ATX. Permeability and infarct volume were reduced in ERT2 ATX-/- mice compared to ischemia-reperfusion (I/R)-only mice. In addition, the cerebral blood flow was retained in ERT2 ATX-/- compared to I/R mice. The outcomes in the stroke model are alleviated due to the limited LPA concentration, reduced ATX concentration, and ATX activity in ERT2 ATX-/- mice. This study suggests that endothelial-specific ATX leads to increased LPA in the brain vasculature following ischemic-reperfusion and ultimately disrupts vascular permeability, resulting in adverse stroke outcomes.

Electrophilic Aldehyde 4-Hydroxy-2-Nonenal Mediated Signaling and Mitochondrial Dysfunction.

Reactive oxygen species (ROS), a by-product of aerobic life, are highly reactive molecules with unpaired electrons. The excess of ROS leads to oxidative stress, instigating the peroxidation of polyunsaturated fatty acids (PUFA) in the lipid membrane through a free radical chain reaction and the formation of the most bioactive aldehyde, known as 4-hydroxynonenal (4-HNE). 4-HNE functions as a signaling molecule and toxic product and acts mainly by forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and lipids. The mitochondria have been implicated as a site for 4-HNE generation and adduction. Several studies clarified how 4-HNE affects the mitochondria's functions, including bioenergetics, calcium homeostasis, and mitochondrial dynamics. Our research group has shown that 4-HNE activates mitochondria apoptosis-inducing factor (AIFM2) translocation and facilitates apoptosis in mice and human heart tissue during anti-cancer treatment. Recently, we demonstrated that a deficiency of SOD2 in the conditional-specific cardiac knockout mouse increases ROS, and subsequent production of 4-HNE inside mitochondria leads to the adduction of several mitochondrial respiratory chain complex proteins. Moreover, we highlighted the physiological functions of HNE and discussed their relevance in human pathophysiology and current discoveries concerning 4-HNE effects on mitochondria.

Can technology and the media help reduce dysfunctional parenting and increase engagement with preventative parenting interventions?

In an evaluation of the television series "Driving Mum and Dad Mad," 723 families participated and were randomly assigned to either a standard or technology enhanced viewing condition (included additional Web-support). Parents in both conditions reported significant improvements from pre- to postintervention in their child's behavior, dysfunctional parenting, parental anger, depression, and self-efficacy. Short-term improvements were maintained at 6-months follow-up. Regressions identified predictors of program outcomes and level of involvement. Parents who watched the entire series had more severe problems at preintervention and high sociodemographic risk than parents who did not watch the entire series. Few sociodemographic, child, or parent variables assessed at preintervention predicted program outcomes or program engagement, suggesting that a wide range of parents from diverse socioeconomic status benefited from the program. Media interventions depicting evidence-based parenting programs may be a useful means of reaching hard to engage families in population-level child maltreatment prevention programs.

The generation of a novel polyoxometalate-based 3D framework following picolinate-chelation of tungsten and potassium centres.

A new polyoxometalate-based 3D framework K(5)Na[K(2){Dy(H(2)O)(3)}(2){As(2)W(19)O(68)}{WO(2)(pic)}(2)] (1) (pic = 2-picolinate), composed of picolinate-functionalised dysprosium-containing tungstoarsenates and distorted potassium-picolinate cubane units, has been synthesised from the polyoxometalate precursor [As(2)W(19)O(67)(H(2)O)](14-).

A new parenting-based group intervention for young anxious children: results of a randomized controlled trial.

OBJECTIVE: Despite recent advances, there are still no interventions that have been developed for the specific treatment of young children who have anxiety disorders. This study examined the impact of a new, cognitive-behaviorally based parenting intervention on anxiety symptoms. METHOD: Families of 74 anxious children (aged 9 years or less) took part in a randomized controlled trial, which compared the new 10-session, group-format intervention with a wait-list control condition. Outcome measures included blinded diagnostic interview and self-reports from parents and children. RESULTS: Intention-to-treat analyses indicated that children whose parent(s) received the intervention were significantly less anxious at the end of the study than those in the control condition. Specifically, 57% of those receiving the new intervention were free of their primary disorder, compared with 15% in the control condition. Moreover, 32% of treated children were free of any anxiety diagnosis at the end of the treatment period, compared with 6% of those in the control group. Treatment gains were maintained at 12-month follow-up. CONCLUSIONS: This new parenting-based intervention may represent an advance in the treatment of this previously neglected group.