Beyond the electrical double layer model: ion-dependent effects in nanoscale solvent organization.

The nanoscale organization of electrolyte solutions at interfaces is often described well by the electrical double-layer model. However, a recent study has shown that this model breaks down in solutions of LiClO4 in acetonitrile at a silica interface, because the interface imposes a strong structuring in the solvent that in turn determines the preferred locations of cations and anions. As a surprising consequence of this organisation, the effective surface potential changes from negative at low electrolyte concentration to positive at high electrolyte concentration. Here we combine previous ion-current measurements with vibrational sum-frequency-generation spectroscopy experiments and molecular dynamics simulations to explore how the localization of ions at the acetonitrile-silica interface depends on the sizes of the anions and cations. We observe a strong, synergistic effect of the cation and anion identities that can prompt a large difference in the ability of ions to partition to the silica surface, and thereby influence the effective surface potential. Our results have implications for a wide range of applications that involve electrolyte solutions in polar aprotic solvents at nanoscale interfaces.

Physical activity, suicidal ideation, suicide attempt and death among individuals with mental or other medical disorders: A systematic review of observational studies.

A growing body of research has demonstrated the potential role for physical activity as an intervention across mental and other medical disorders. However, the association between physical activity and suicidal ideation, attempts, and deaths has not been systematically appraised in clinical samples. We conducted a PRISMA 2020-compliant systematic review searching MEDLINE, EMBASE, and PsycINFO for observational studies investigating the influence of physical activity on suicidal behavior up to December 6, 2023. Of 116 eligible full-text studies, seven (n = 141691) were included. Depression was the most frequently studied mental condition (43%, k = 3), followed by chronic pain as the most common other medical condition (29%, k = 2). Two case-control studies examined suicide attempts and found an association between physical activity and a reduced frequency of such attempts. However, in studies examining suicidal ideation (k = 3) or suicide deaths (k = 2), no consistent associations with physical activity were observed. Overall, our systematic review found that physical activity may be linked to a lower frequency of suicide attempts in non-prospective studies involving individuals with mental disorders.

Toxicokinetics of thebaine in those consuming non-food grade poppy seeds as a tea.

INTRODUCTION: Thebaine is an alkaloid in poppy seeds that is neurotoxic to animals. Data on its clinical effects and toxicokinetics in people are minimal. In 2022, poppy seeds high in thebaine entered the Australian food market, and people consuming tea made from these poppy seeds developed poisoning. METHODS: Three patients who drank poppy seed tea and developed neuromuscular toxicity consented for thebaine to be quantitated in serial blood samples. Blood samples were analyzed by liquid chromatography with high-resolution mass spectrometry. RESULTS: Case 1: A man in his 60s presented with drowsiness, vomiting, malaise and myoclonus. He developed metabolic acidosis with hyperlactataemia, acute kidney injury requiring haemodialysis, convulsions, rhabdomyolysis, and was in the hospital for 18 days. The admission thebaine blood concentration was 2.1 mg/L, and the apparent elimination half-life was 14.8 h. Case 2: A man in his 30s presented with myoclonus, rigidity, vomiting, and dizziness. He developed metabolic acidosis with hyperlactataemia, acute kidney injury, and myalgias. The admission thebaine blood concentration was 4.1 mg/L, and the apparent elimination half-life was 11.6 h. Case 3: A man in his 30s presented with myoclonus, rigidity, clonus, diaphoresis, and abdominal pain. The admission thebaine blood concentration was 2.2 mg/L, and the apparent elimination half-life was 8.3 h. DISCUSSION: Neuromuscular toxicity, metabolic acidosis with hyperlactataemia, acute kidney injury, and gastrointestinal symptoms were prominent clinical features in these patients after drinking poppy seed tea. Effects persisted for days, and all survived, despite thebaine concentrations far exceeding those in published forensic reports, although human data are sparse. Compared to rats, the thebaine apparent elimination half-life is much longer in humans who develop symptoms at lower concentrations. CONCLUSIONS: Despite relatively high thebaine blood concentrations and moderate to severe poisoning, outcomes were favourable with early presentations. It is possible that acute kidney injury prolongs the apparent elimination half-life of thebaine.

The role of oxygen incorporation in Ni (111) substrates on the growth of hexagonal boron nitride monolayers.

Reliable and controllable growth of two-dimensional (2D) hexagonal boron nitride (h-BN) is essential for its wide range of applications. Substrate engineering is one of the critical factors that influence the growth of the epitaxial h-BN films. Here, we report the growth of monolayer h-BN on Ni (111) substrates incorporated with oxygen atoms via molecular beam epitaxy. It was found that the increase of incorporated oxygen concentration in the Ni substrate through a pretreatment process prior to the h-BN growth step would have an adverse effect on the morphology and growth rate of 2D h-BN. Under the same growth condition, h-BN monolayer coverage decreases exponentially as the amount of oxygen incorporated into Ni (111) increases. Density functional theory calculations and climbing image nudged elastic band (CI-NEB) method reveal that the substitutional oxygen atoms can increase the diffusion energy barrier of B and N atoms on Ni (111) thereby inhibiting the growth of h-BN films. As-grown large-area h-BN monolayer films and fabricated Al/h-BN/Ni (MIM) nanodevices were comprehensively characterized to evaluate the structural, optical and electrical properties of high-quality monolayers. Direct tunneling mechanism and high breakdown strength of ∼11.2 MV cm-1are demonstrated for the h-BN monolayers grown on oxygen-incorporated Ni (111) substrates, indicating that these films have high quality. This study provides a unique example that heterogeneous catalysis principles can be applied to the epitaxy of 2D crystals in solid state field. Similar strategies can be used to grow other 2D crystalline materials, and are expected to facilitate the development of next generation devices based on 2D crystals.

Breast cancer 1 (BRCA1) protection in altered gene expression and neurodevelopmental disorders due to physiological and ethanol-enhanced reactive oxygen species formation.

The breast cancer 1 (Brca1) susceptibility gene regulates the repair of reactive oxygen species (ROS)-mediated DNA damage, which is implicated in neurodevelopmental disorders. Alcohol (ethanol, EtOH) exposure during pregnancy causes fetal alcohol spectrum disorders (FASD), including abnormal brain function, associated with enhanced ROS-initiated DNA damage. Herein, oxidative DNA damage in fetal brains and neurodevelopmental disorders were enhanced in saline-exposed +/- vs. +/+ Brca1 littermates. A single EtOH exposure during gestation further enhanced oxidative DNA damage, altered the expression of developmental/DNA damage response genes in fetal brains, and resulted in neurodevelopmental disorders, all of which were BRCA1-dependent. Pretreatment with the ROS inhibitor phenylbutylnitrone (PBN) blocked DNA damage and some neurodevelopmental disorders in both saline- and EtOH-exposed progeny, corroborating a ROS-dependent mechanism. Fetal BRCA1 protects against altered gene expression and neurodevelopmental disorders caused by both physiological and EtOH-enhanced levels of ROS formation. BRCA1 deficiencies may enhance the risk for FASD.

A systematic review of perioperative clinical practice guidelines for care of older adults living with frailty.

BACKGROUND: Perioperative frailty is prevalent and requires complex management, which could be guided by clinical practice guidelines (CPGs). The objective of this systematic review was to identify and synthesise CPGs that provide perioperative recommendations specific to older adults living with frailty. METHODS: After protocol registration, we performed a systematic review of CPGs. MEDLINE, Embase, CINAHL, and 14 grey literature databases were searched (January 1, 2000 until December 22, 2021). We included all CPGs that contained at least one frailty-specific recommendation related to any phase of the perioperative period. We compiled all relevant recommendations, extracted underlying strength of evidence, and categorised them by perioperative phase of care. Within each phase, recommendations were synthesised inductively into themes. Quality of CPGs was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. RESULTS: From 4707 citations, 13 guidelines were included; 8/13 were focused on the perioperative care of older surgical patients in general. Among 110 recommendations extracted, 37 themes were generated, with the majority pertaining to preoperative care. Four themes were supported by strong evidence: performing preoperative frailty assessments, using multidimensional frailty instruments, reducing urinary catheter use, and following multidisciplinary care and communication throughout the perioperative period. Per AGREE II, most guidelines (8/13; 62%) were recommended for use with modifications. CONCLUSIONS: Despite increasing numbers of patients living with frailty, few guidelines exist that address frailty-specific perioperative care. Given the lack of strong evidence-based recommendations, particularly outside the preoperative period, high-quality primary research is required to underpin future guidelines and better inform the care of older surgical patients with frailty. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42022320149.

Acute chorioamnionitis in pregnancies complicated by placental abruption and short-term neonatal outcomes: A retrospective cohort study.

We examined neonatal outcomes in pregnancies complicated by placental abruption (PA) and acute chorioamnionitis (CA). Exposure was acute CA; primary outcome - fetal death; secondary outcomes - adverse Apgar score, neonatal intensive care unit (NICU) admission, and cardiac depression. 267 placentas - 18.4% exhibited acute CA. PA pregnancies with CA - 29% experienced fetal death. Funisitis, acute CA and adverse neonatal outcomes are dependent. Without accounting for funisitis, aforementioned findings hold, though effect sizes are smaller. PA, acute CA with funisitis could affect fetal death and NICU admission. Acute CA and PA alone could impact fetal death and adverse Apgar scores.

The promise of machine learning applications in solid organ transplantation.

Solid-organ transplantation is a life-saving treatment for end-stage organ disease in highly selected patients. Alongside the tremendous progress in the last several decades, new challenges have emerged. The growing disparity between organ demand and supply requires optimal patient/donor selection and matching. Improvements in long-term graft and patient survival require data-driven diagnosis and management of post-transplant complications. The growing abundance of clinical, genetic, radiologic, and metabolic data in transplantation has led to increasing interest in applying machine-learning (ML) tools that can uncover hidden patterns in large datasets. ML algorithms have been applied in predictive modeling of waitlist mortality, donor-recipient matching, survival prediction, post-transplant complications diagnosis, and prediction, aiming to optimize immunosuppression and management. In this review, we provide insight into the various applications of ML in transplant medicine, why these were used to evaluate a specific clinical question, and the potential of ML to transform the care of transplant recipients. 36 articles were selected after a comprehensive search of the following databases: Ovid MEDLINE; Ovid MEDLINE Epub Ahead of Print and In-Process & Other Non-Indexed Citations; Ovid Embase; Cochrane Database of Systematic Reviews (Ovid); and Cochrane Central Register of Controlled Trials (Ovid). In summary, these studies showed that ML techniques hold great potential to improve the outcome of transplant recipients. Future work is required to improve the interpretability of these algorithms, ensure generalizability through larger-scale external validation, and establishment of infrastructure to permit clinical integration.

Rapid cognitive assessment tools for screening of mild cognitive impairment in the preoperative setting: A systematic review and meta-analysis.

IMPORTANCE: Mild cognitive impairment (MCI) is a high-risk precursor to dementia, post-operative delirium, and prolonged hospitalization. There is a need for preoperative rapid cognitive screening tools. STUDY OBJECTIVE: To evaluate the predictive parameters of rapid MCI screening tools in different clinical settings for preoperative application. DESIGN: Systematic review and meta-analyses searching Medline, and other databases from inception to May 26, 2021. The Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines were followed for data curation and quality assessment. Title and abstract screening were conducted independently via Rayyan. Data was curated through a random-effects model and statistical analysis used R-software. SETTING: Community, memory clinic, emergency, long-term care, and in-patient settings. There were no studies in the preoperative setting. PATIENTS: Twenty-three studies with 9973 patients (≥ 60 years old) undergoing rapid MCI screening. INTERVENTION: Rapid (≤ 5 min) MCI screening tools. MEASUREMENTS: Pooled predictive parameters (sensitivity, specificity) of screening tests. MAIN RESULTS: Eighteen screening tools, compared to neuropsychological tests, were identified. The overall prevalence of MCI among the Rapid Cognitive Screen (RCS), Six-item Screener (SIS), Mini-Cog, and Clock Drawing Test (CDT) studies were 24.6%, 28.3%, 40.9%, and 20.7%, respectively. RCS has 82% sensitivity and 79% specificity in detecting MCI. SIS has 61% sensitivity and 89% specificity. Mini-Cog has 52% sensitivity and 80% specificity. CDT has 56% sensitivity and 59% specificity. Seven other index tools had high sensitivities of 97%-82% and specificities of 90%-73% but were studied only once. CONCLUSION: No rapid screening tools had been validated in the surgical population. In other populations, RCS may be a promising screening tool for MCI with stronger sensitivity and specificity than Mini-Cog, SIS, and CDT. CDT alone is ineffective for MCI detection. Further validation in the preoperative setting is required to determine the efficacy of these screening tools.

Application of machine learning in liver transplantation: a review.

BACKGROUND: Machine learning (ML) has been increasingly applied in the health-care and liver transplant setting. The demand for liver transplantation continues to expand on an international scale, and with advanced aging and complex comorbidities, many challenges throughout the transplantation decision-making process must be better addressed. There exist massive datasets with hidden, non-linear relationships between demographic, clinical, laboratory, genetic, and imaging parameters that conventional methods fail to capitalize on when reviewing their predictive potential. Pre-transplant challenges include addressing efficacies of liver segmentation, hepatic steatosis assessment, and graft allocation. Post-transplant applications include predicting patient survival, graft rejection and failure, and post-operative morbidity risk. AIM: In this review, we describe a comprehensive summary of ML applications in liver transplantation including the clinical context and how to overcome challenges for clinical implementation. METHODS: Twenty-nine articles were identified from Ovid MEDLINE, MEDLINE Epub Ahead of Print and In-Process and Other Non-Indexed Citations, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. CONCLUSION: ML is vastly interrogated in liver transplantation with promising applications in pre- and post-transplant settings. Although challenges exist including site-specific training requirements, the demand for more multi-center studies, and optimization hurdles for clinical interpretability, the powerful potential of ML merits further exploration to enhance patient care.

Impact of Co-Existing Placental Pathologies in Pregnancies Complicated by Placental Abruption and Acute Neonatal Outcomes.

Placental abruption (PA) is a concern for maternal and neonatal morbidity. Adverse neonatal outcomes in the setting of PA include higher risk of prematurity. Placental pathologies include maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), acute chorioamnionitis, and villitis of unknown etiology (VUE). We aimed to investigate how placental pathology contributes to acute neonatal outcome in PA. A retrospective cohort study of all placentas with PA were identified. Exposures were MVM, FVM, acute chorioamnionitis and VUE. The primary outcome was NICU admission and the secondary outcomes included adverse base deficit and Apgar scores, need for resuscitation, and small-for-gestational age. A total of 287 placentas were identified. There were 160 (59.9%) of placentas with PA alone vs 107 (40.1%) with PA and additional placental pathologies. Odds of NICU admission were more than two times higher in pregnancies with placental pathologies (OR = 2.37, 95% CI 1.28-4.52). These estimates were in large part mediated by prematurity and birthweight, indirect effect acting through prematurity was OR 1.79 (95% CI 1.12-2.75) and through birthweight OR 2.12 (95% CI 1.40-3.18). Odds of Apgar score ≤ 5 was more than four times higher among pregnancies with placental pathologies (OR = 4.56, 95% CI 1.28-21.26). Coexisting placental pathology may impact Apgar scores in pregnancies complicated by PA. This knowledge could be used by neonatal teams to mobilize resources in anticipation of the need for neonatal resuscitation.

Impact of SARS-CoV-2 on the clinical outcomes and placental pathology of pregnant women and their infants: A systematic review.

Pregnant women are susceptible to viral infections due to physiological changes such as cell-mediated immunity. No severe adverse pregnancy or neonatal outcomes have been consistently reported in 2019 novel coronavirus disease (COVID-19) positive pregnancy cases. There are controversies around the role of COVID-19 in pregnancy. A systematic review was conducted to examine clinical maternal and neonatal clinical outcomes. Studies were included if they reported SARS-CoV-2 infection among pregnant women and/or COVID-19 positive neonates as validated by positive antibody testing or viral testing using polymerase chain reaction. Case series, case reports, case-control studies, and comparative studies were included. Eight hundred and thirty-seven records were identified, resulting in 525 records for level I screening. Forty-one were included after full-text review. Results suggest elevated rates of intensive care unit (ICU) admission, gestational diabetes, preeclampsia, C-sections, pre-term birth, and C-reactive protein (CRP) in comparison to pregnant women without SARS-CoV-2. Careful monitoring of pregnancies with SARS-CoV-2 is recommended.

A Chest-Laminated Ultrathin and Stretchable E-Tattoo for the Measurement of Electrocardiogram, Seismocardiogram, and Cardiac Time Intervals.

Seismocardiography (SCG) is a measure of chest vibration associated with heartbeats. While skin soft electronic tattoos (e-tattoos) have been widely reported for electrocardiogram (ECG) sensing, wearable SCG sensors are still based on either rigid accelerometers or non-stretchable piezoelectric membranes. This work reports an ultrathin and stretchable SCG sensing e-tattoo based on the filamentary serpentine mesh of 28-µm-thick piezoelectric polymer, polyvinylidene fluoride (PVDF). 3D digital image correlation (DIC) is used to map chest vibration to identify the best location to mount the e-tattoo and to investigate the effects of substrate stiffness. As piezoelectric sensors easily suffer from motion artifacts, motion artifacts are effectively reduced by performing subtraction between a pair of identical SCG tattoos placed adjacent to each other. Integrating the soft SCG sensor with a pair of soft gold electrodes on a single e-tattoo platform forms a soft electro-mechano-acoustic cardiovascular (EMAC) sensing tattoo, which can perform synchronous ECG and SCG measurements and extract various cardiac time intervals including systolic time interval (STI). Using the EMAC tattoo, strong correlations between STI and the systolic/diastolic blood pressures, are found, which may provide a simple way to estimate blood pressure continuously and noninvasively using one chest-mounted e-tattoo.

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.

Fast reflective optic-based rotational anisotropy nonlinear harmonic generation spectrometer.

We present a novel Rotational Anisotropy Nonlinear Harmonic Generation (RA-NHG) apparatus based primarily upon reflective optics. The data acquisition scheme used here allow for fast accumulation of RA-NHG traces, mitigating low frequency noise from laser drift, while permitting real-time adjustment of acquired signals with significantly more data points per unit angle rotation of the optics than other RA-NHG setups. We discuss the design and construction of the optical and electronic components of the device and present example data taken on a GaAs test sample at a variety of wavelengths. The RA-second harmonic generation data for this sample show the expected four-fold rotational symmetry across a broad range of wavelengths, while those for RA-third harmonic generation exhibit evidence of cascaded nonlinear processes possible in acentric crystal structures.

tagPAINT: covalent labelling of genetically encoded protein tags for DNA-PAINT imaging.

Recently, DNA-PAINT single-molecule localization microscopy (SMLM) has shown great promise for quantitative imaging; however, labelling strategies thus far have relied on multivalent and affinity-based approaches. Here, the covalent labelling of expressed protein tags (SNAP tag and Halo tag) with single DNA-docking strands and application of SMLM via DNA-PAINT is demonstrated. tagPAINT is then used for T-cell receptor signalling proteins at the immune synapse as a proof of principle.

Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells.

Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.