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Abstract Measurements and imaging of the mechanical response of biological cells are critical for understanding the mechanisms of many diseases, and for fundamental studies of energy, signal and force transduction. The recent emergence of Brillouin microscopy as a powerful non-contact, label-free way to non-invasively and non-destructively assess local viscoelastic properties provides an opportunity to expand the scope of biomechanical research to the sub-cellular level. Brillouin spectroscopy has recently been validated through static measurements of cell viscoelastic properties, however, fast (sub-second) measurements of sub-cellular cytomechanical changes have yet to be reported. In this report, we utilize a custom multimodal spectroscopy system to monitor for the very first time the rapid viscoelastic response of cells and subcellular structures to a short-duration electrical impulse. The cytomechanical response of three subcellular structures - cytoplasm, nucleoplasm, and nucleoli - were monitored, showing distinct mechanical changes despite an identical stimulus. Through this pioneering transformative study, we demonstrate the capability of Brillouin spectroscopy to measure rapid, real-time biomechanical changes within distinct subcellular compartments. Our results support the promising future of Brillouin spectroscopy within the broad scope of cellular biomechanics.

Abstract Previous work demonstrated inactivation of influenza virus by GHz frequency electromagnetic fields. Despite theoretical and experimental results, the underlying mechanism driving this inactivation remains unknown. One hypothesis is that the electromagnetic field is causing damage to the virion membrane (and therefore changing spike protein orientation) rendering the virus unable to attach and infect host cells. Towards examining this hypothesis, our group employed nanosecond pulsed electric fields (nsPEFs) as a surrogate to radiofrequency (RF) exposure to enable exploration of dose response thresholds of electric field-induced viral membrane damage. In summary, Bovine coronavirus (BCoV) was exposed, in suspension, to mono and bipolar 600-ns pulsed electric fields (nsPEFs) at two amplitudes (12.5 and 25 kV/cm) and pulse numbers [0 (sham), 1, 5, 10, 100, and 1000] at a 1 Hz (Hz) repetition rate. The temperature rise immediately after exposure(s) was measured using thermocouples to differentiate effects of the electric field (E-field) and heating (i.e., the thermal gradient). Inactivation of BCoV was evaluated by infecting HRT-18G host cells and assessing differences in virus infectivity days after exposure. Our results show that 600 nsPEFs, both bipolar and monopolar, can reduce the infectivity of coronaviruses at various amplitudes, pulse numbers, and pulse polarity. Interestingly, we observed that bipolar exposures appeared to be more efficient at lower exposure intensities than monopolar pulses. Future work should focus on experiments to identify the mechanism underlying nsPEF-induced viral inactivation.

Abstract Inactivation of influenza A virus by radiofrequency (RF) energy exposure at levels near Institute of Electrical and Electronics Engineers (IEEE) safety thresholds has been reported. The authors hypothesized that this inactivation was through a structure-resonant energy transfer mechanism. If this hypothesis is confirmed, such a technology could be used to prevent transmission of virus in occupied public spaces where RF irradiation of surfaces could be performed at scale. The present study aims to both replicate and expand the previous work by investigating the neutralization of bovine coronavirus (BCoV), a surrogate of SARS-CoV-2, by RF radiation in 6–12 GHz range. Results showed an appreciable reduction in BCoV infectivity (up to 77%) due to RF exposure to certain frequencies, but failed to generate enough reduction to be considered clinically significant.

Abstract Single-cell analysis, or cytometry, is a ubiquitous tool in the biomedical sciences. Whereas most cytometers use fluorescent probes to ascertain the presence or absence of targeted molecules, biophysical parameters such as the cell density, refractive index, and viscosity are difficult to obtain. In this work, we combine two complementary techniques—quantitative phase imaging and Brillouin spectroscopy—into a label-free image cytometry platform capable of measuring more than a dozen biophysical properties of individual cells simultaneously. Using a geometric simplification linked to freshly plated cells, we can acquire the cellular diameter, volume, refractive index, mass density, non-aqueous mass, fluid volume, dry volume, the fractional water content of cells, both by mass and by volume, the Brillouin shift, Brillouin linewidth, longitudinal modulus, longitudinal viscosity, the loss modulus, and the loss tangent, all from a single acquisition, and with no assumptions of underlying parameters. Our methods are validated across three cell populations, including a control population of CHO-K1 cells, cells exposed to tubulin-disrupting nocodazole, and cells under hypoosmotic shock. Our system will unlock new avenues of research in biophysics, cell biology, and medicine.

Measurement(s) Cognition • Psychiatric Diagnosis • Development Technology Type(s) MRI • phenotypic battery • actigraphy • laboratory analysis Sample Characteristic - Organism Homo sapien Sample Characteristic - Environment Community-ascertained non-diagnostic sample Sample Characteristic - Location United States

Abstract Exposures to radiofrequency electromagnetic fields (RF-EMFs, 100 kHz to 6 GHz) have been associated with both positive and negative effects on cognitive behavior. To elucidate the mechanism of RF-EMF interaction, a few studies have examined its impact on neuronal activity and synaptic plasticity. However, there is still a need for additional basic research that further our understanding of the underlying mechanisms of RF-EMFs on the neuronal system. The present study investigated changes in neuronal activity and synaptic transmission following a 60-min exposure to 3.0 GHz RF-EMF at a low dose (specific absorption rate (SAR)

Tip-of-the-tongue states are subjective experiences that unrecalled target words will be remembered. This study investigates if the visual fluency of familiar faces affects the likelihood of tip-of-the-tongue experiences (TOTs) as well as name recall and name recognition. To manipulate visual fluency, three levels of clarity for 396 celebrity faces were set: high, medium, and low clarity. Four hundred and twenty-nine participants were asked to recall the last names of the celebrities for all clarity levels, and, if they did not recall, to indicate if they experienced a TOT. Following the TOT question, they performed a name recognition test. Results showed that higher-clarity faces resulted in higher TOT rates than lower-clarity faces for unrecalled faces. Name recall was also higher for clearer faces. However, clarity level did not affect the correct answer rate on the name recognition test. These results support the view that perceptual cue-based factors influence TOT experiences.

Reversing the pulse polarity, i.e., changing the electric field direction by 180°, inhibits electroporation and electrostimulation by nanosecond electric pulses (nsEPs). This feature, known as “bipolar cancellation,” enables selective remote targeting with nsEPs and reduces the neuromuscular side effects of ablation therapies. We analyzed the biophysical mechanisms and measured how cancellation weakens and is replaced by facilitation when nsEPs are applied from different directions at angles from 0 to 180°. Monolayers of endothelial cells were electroporated by a train of five pulses (600 ns) or five paired pulses (600 + 600 ns) applied at 1 Hz or 833 kHz. Reversing the electric field in the pairs (180° direction change) caused 2-fold (1 Hz) or 20-fold (833 kHz) weaker electroporation than the train of single nsEPs. Reducing the angle between pulse directions in the pairs weakened cancellation and replaced it with facilitation at angles

Introduction/Objectives: Due to the risks associated with sedative hypnotic medications in older adults, our study evaluated the impact of a multidisciplinary approach to deprescribing in geriatric primary care clinics. Methods: The study was a retrospective review of older adults at 2 academic, geriatric primary care clinics who were prescribed sedative-hypnotic medications. Patients were mailed an education packet of information that included working with the clinical pharmacy team, behavioral health team, or both in order to deprescribe their sedative-hypnotic medication. The study assessed the rate of discontinuation of sedative-hypnotic medications between the different intervention groups. Results: The study included 93 older adults with a mean age of 81.3 years and 39.8% discontinuation rate of their medication. The number of falls decreased in patients who discontinued use compared to when previously using a sedative hypnotic medication. Conclusion: Patients are more likely to discontinue their sedative hypnotic medication with a multidisciplinary approach, specifically with primary care provider support.

Abstract Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

The leading cause of treatment failure in Staphylococcus aureus infections is the development of biofilms. Biofilms are highly tolerant to conventional antibiotics which were developed against planktonic cells. Consequently, there is a lack of antibiofilm agents in the antibiotic development pipeline. To address this problem, we developed a platelet-rich plasma (PRP)-derived biologic, termed BIO-PLY (for the BIOactive fraction of Platelet-rich plasma LYsate) which has potent in vitro bactericidal activity against S. aureus synovial fluid free-floating biofilm aggregates. Additional in vitro studies using equine synoviocytes and chondrocytes showed that BIO-PLY protected these cells of the joint from inflammation. The goal of this study was to test BIO-PLY for in vivo efficacy using an equine model of infectious arthritis. We found that horses experimentally infected with S. aureus and subsequently treated with BIO-PLY combined with the antibiotic amikacin (AMK) had decreased bacterial concentrations within both synovial fluid and synovial tissue and exhibited lower systemic and local inflammatory scores compared to horses treated with AMK alone. Most importantly, AMK+BIO-PLY treatment reduced the loss of infection-associated cartilage proteoglycan content in articular cartilage and decreased synovial tissue fibrosis and inflammation. Our results demonstrate the in vivo efficacy of AMK+BIO-PLY and represents a new approach to restore and potentiate antimicrobial activity against synovial fluid biofilms.

Abstract Background Nearly half of all mental health disorders develop prior to the age of 15. Early assessments, diagnosis, and treatment are critical to shortening single episodes of care, reducing possible comorbidity and long-term disability. In Norway, approximately 20% of all children and adolescents are experiencing mental health problems. To address this, health officials in Norway have called for the integration of innovative approaches. A clinical decision support system (CDSS) is an innovative, computer-based program that provides health professionals with clinical decision support as they care for patients. CDSS use standardized clinical guidelines and big data to provide guidance and recommendations to clinicians in real-time. IDDEAS (Individualised Digital DEcision Assist System) is a CDSS for diagnosis and treatment of child and adolescent mental health disorders. The aim of IDDEAS is to enhance quality, competency, and efficiency in child and adolescent mental health services (CAMHS). Methods/design IDDEAS is a mixed-methods innovation and research project, which consists of four stages: 1) Assessment of Needs and Preparation of IDDEAS; 2) The Development of IDDEAS CDSS Model; 3) The Evaluation of the IDDEAS CDSS; and, 4) Implementation & Dissemination. Both qualitative and quantitative methods will be used for the evaluation of IDDEAS CDSS model. Child and adolescent psychologists and psychiatrists (n = 30) will evaluate the IDDEAS` usability, acceptability and relevance for diagnosis and treatment of attention-deficit/hyperactivity disorder. Discussion The IDDEAS CDSS model is the first guidelines and data-driven CDSS to improve efficiency of diagnosis and treatment of child and adolescent mental health disorders in Norway. Ultimately, IDDEAS will help to improve patient health outcomes and prevent long-term adverse outcomes by providing each patient with evidence-based, customized clinical care. Trial registration ISRCTN, ISRCTN12094788. Ongoing study, registered prospectively 8 April 2020 https://doi.org/10.1186/ISRCTN12094788

Abstract Background This paper is a systematic review and meta-analysis of the efficacy of available medications for the treatment of restricted/repetitive behavior (RRBs) in Autism Spectrum Disorder (ASD). Method We searched MEDLINE, Embase, PsycINFO, The Cochrane Library (Cochrane Database of Systematic Reviews (CDRS), the Cochrane Central Register of Controlled Trials (CENTRAL), database of Abstracts of Reviews of Effects (DARE)), Scopus, Epistimonikos, Clinicaltrials.gov, and included all randomized controlled trials published after 1993 that were directed at RRBs in patients with ASD of all ages. We extracted the relevant data from the published studies with a predefined data extraction form and assessed the risk of bias. The primary outcomes were change in restricted/repetitive behavior. We performed a meta-analysis using the random effect model and included studies with given mean and standard deviation. This study is registered with PROSPERO number CRD42018092660). Results We identified 14 randomized controlled trials that met initial inclusion criteria. After closer inspection, nine trials – involving 552 patients in total – were included in the final analysis. The meta-analysis found no significant difference between medications (including fluvoxamine, risperidone, fluoxetine, citalopram, oxytocin, N-Acetylcysteine, buspirone) and placebo in the treatment of RRBs in ASD (P = 0.20). Similarly, the sub-group meta-analysis also showed no significant difference between Selective Serotonin Reuptake Inhibitor (SSRIs) and placebo in the treatment of RRBs in ASD (P = 0.68). There was no evidence of publication bias. Conclusion This meta-analysis finds little support for the routine use of medications to treat restricted/repetitive behaviors in Autism Spectrum Disorder. Further research of large, balanced trials with precise assessment tools and long-term follow-up are needed. Trial registration The study protocol is registered in PROSPERO (Reference number: CRD42018092660) .

Abstract Cell suspensions of Escherichia coli and Lactobacillus acidophilus were exposed to 600-ns pulsed electric fields (nsPEFs) at varying amplitudes (Low-13.5, Mid-18.5 or High-23.5 kV cm−1) and pulse numbers (0 (sham), 1, 5, 10, 100 or 1000) at a 1 hertz (Hz) repetition rate. The induced temperature rise generated at these exposure parameters, hereafter termed thermal gradient, was measured and applied independently to cell suspensions in order to differentiate inactivation triggered by electric field (E-field) from heating. Treated cell suspensions were plated and cellular inactivation was quantified by colony counts after a 24-hour (h) incubation period. Additionally, cells from both exposure conditions were incubated with various antibiotic-soaked discs to determine if nsPEF exposure would induce changes in antibiotic susceptibility. Results indicate that, for both species, the total delivered energy (amplitude, pulse number and pulse duration) determined the magnitude of cell inactivation. Specifically, for 18.5 and 23.5 kV cm−1 exposures, L. acidophilus was more sensitive to the inactivation effects of nsPEF than E. coli, however, for the 13.5 kV cm−1 exposures E. coli was more sensitive, suggesting that L. acidophilus may need to meet an E-field threshold before significant inactivation can occur. Results also indicate that antibiotic susceptibility was enhanced by multiple nsPEF exposures, as observed by increased zones of growth inhibition. Moreover, for both species, a temperature increase of ≤ 20 °C (89% of exposures) was not sufficient to significantly alter cell inactivation, whereas none of the thermal equivalent exposures were sufficient to change antibiotic susceptibility categories.

Cancer ablation therapies aim to be efficient while minimizing damage to healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising ablation modality because of its selectivity against certain cell types and reduced neuromuscular effects. We compared cell killing efficiency by PEF (100 pulses, 200 ns–10 µs duration, 10 Hz) in a panel of human esophageal cells (normal and pre-malignant epithelial and smooth muscle). Normal epithelial cells were less sensitive than the pre-malignant ones to unipolar PEF (15–20% higher LD50, p < 0.05). Smooth muscle cells (SMC) oriented randomly in the electric field were more sensitive, with 30–40% lower LD50 (p < 0.01). Trains of ten, 300-ns pulses at 10 kV/cm caused twofold weaker electroporative uptake of YO-PRO-1 dye in normal epithelial cells than in either pre-malignant cells or in SMC oriented perpendicularly to the field. Aligning SMC with the field reduced the dye uptake fourfold, along with a twofold reduction in Ca2+ transients. A 300-ns pulse induced a twofold smaller transmembrane potential in cells aligned with the field, making them less vulnerable to electroporation. We infer that damage to SMC from nsPEF ablation of esophageal malignancies can be minimized by applying the electric field parallel to the predominant SMC orientation.

Many critical aspects of contemporary human cognitive functionality (e.g., reading, fixing a car) evolved historically in a time frame that biological natural selection cannot account for. Because of this, the best way to understand the factors that may have led to human cognition evolution is to look at cognitive processes in non-human primates. I argue here that comparative approaches are successful in informing us about human cognitive evolution. Furthermore, making predictions based on natural ecology will allow us to explore comparative cognition in a manner that avoids the trend to determine if non-human primates simply can do what we do. Instead, we can track different patterns of natural selection by examining how cognition differs across specific ecological niches. In this essay, I write of the excellent work applying foraging ecology to spatial memory. I then consider the ways in which metacognition has been addressed in humans and non-human primates and apply the logic of looking for differences based on ecology. Finally, I consider one paradigm that have been used to address the evolution of cognition in humans – survival processing – and discuss how it maps to non-human primates.

Abstract Theories of study time allocation and of curiosity suggest that people are most engaged with and want to devote their time to materials that are not completely mastered but also are not so difficult that they might be impossible. Their curiosity is thought to be triggered by items that are almost known, or are in what is sometimes called the region of proximal learning. Answers that are on the tip-of-the-tongue (TOT)—not immediately recallable but nevertheless evoking a feeling of imminent recall—seem, intuitively, to be materials that have this characteristic of being almost, but not quite, fully known. We therefore, hypothesized that people would be particularly curious to see the answers to questions for which the answers were on the tips of their tongues. To test the TOT curiosity hypothesis, we gave participants 82 general information questions and quickly asked whether the answers were or were not on the tips of their tongues and whether they wanted to see the answers later. Overwhelmingly, items that were accompanied by a TOT feeling were those which evoked participants’ curiosity, regardless of whether the feeling occurred in conjunction with an error of commission, an error of omission, or even with the correct answer.

Background: Exposure of cells to very short (

Cell swelling and blebbing has been commonly observed following nanosecond pulsed electric field (nsPEF) exposure. The hypothesized origin of these effects is nanoporation of the plasma membrane (PM) followed by transmembrane diffusion of extracellular fluid and disassembly of cortical actin structures. This investigation will provide evidence that shows passive movement of fluid into the cell through nanopores and increase of intracellular osmotic pressure are not solely responsible for this observed phenomena. We demonstrate that phosphatidylinositol-4,5-bisphosphate (PIP2) depletion and hydrolysis are critical steps in the chain reaction leading to cellular blebbing and swelling. PIP2 is heavily involved in osmoregulation by modulation of ion channels and also serves as an intracellular membrane anchor to cortical actin and phospholipase C (PLC). Given the rather critical role that PIP2 depletion appears to play in the response of cells to nsPEF exposure, it remains unclear how its downstream effects and, specifically, ion channel regulation may contribute to cellular swelling, blebbing, and unknown mechanisms of the lasting “permeabilization” of the PM.

Optoacoustic (OA) microscopy using an all-optical system based on the probe beam deflection technique (PBDT) for detection of laser-induced acoustic signals was investigated as an alternative to conventional piezoelectric transducers. PBDT provides a number of advantages for OA microscopy including (i) efficient coupling of laser excitation energy to the samples being imaged through the probing laser beam, (ii) undistorted coupling of acoustic waves to the detector without the need for separation of the optical and acoustic paths, (iii) high sensitivity and (iv) ultrawide bandwidth. Because of the unimpeded optical path in PBDT, diffraction-limited lateral resolution can be readily achieved. The sensitivity of the current PBDT sensor of 22 μV/Pa and its noise equivalent pressure (NEP) of 11.4 Pa are comparable with these parameters of the optical micro-ring resonator and commercial piezoelectric ultrasonic transducers. Benefits of the present prototype OA microscope were demonstrated by successfully resolving micron-size details in histological sections of cardiac muscle.

Histological evidence points to the presence of dopamine (DA) in the cephalic sensory organs of multiple gastropod molluscs, suggesting a possible sensory role for the neurotransmitter. We investigated the sensory function of DA in the nudipleuran Pleurobranchaea californica, in which the central neural correlates of sensation and foraging behavior have been well characterized. Tyrosine hydroxylase-like immunoreactivity (THli), a signature of the dopamine synthetic pathway, was similar to that found in two other opisthobranchs and two pulmonates previously studied: 1) relatively few (

Nanosecond electrical pulse (nsEP) exposure activates signaling pathways, produces oxidative stress, stimulates hormone secretion, causes cell swelling and induces apoptotic and necrotic death. The underlying biophysical connection(s) between these diverse cellular reactions and nsEP has yet to be elucidated. Using global genetic analysis, we evaluated how two commonly studied cell types, U937 and Jurkat, respond to nsEP exposure. We hypothesized that by studying the genetic response of the cells following exposure, we would gain direct insight into the stresses experienced by the cell and in turn better understand the biophysical interaction taking place during the exposure. Using Ingenuity Systems software, we found genes associated with cell growth, movement and development to be significantly up-regulated in both cell types 4 h post exposure to nsEP. In agreement with our hypothesis, we also found that both cell lines exhibit significant biological changes consistent with mechanical stress induction. These results advance nsEP research by providing strong evidence that the interaction of nsEPs with cells involves mechanical stress.

Above a threshold electric field strength, 600 ns-duration pulsed electric field (nsPEF) exposure substantially porates and permeabilizes cellular plasma membranes in aqueous solution to many small ions. Repetitive exposures increase permeabilization to calcium ions (Ca2+) in a dosage-dependent manner. Such exposure conditions can create relatively long-lived pores that reseal after passive lateral diffusion of lipids should have closed the pores. One explanation for eventual pore resealing is active membrane repair, and an ubiquitous repair mechanism in mammalian cells is lysosome exocytosis. A previous study shows that intracellular lysosome movement halts upon a 16.2 kV/cm, 600-ns PEF exposure of a single train of 20 pulses at 5 Hz. In that study, lysosome stagnation qualitatively correlates with the presence of Ca2+ in the extracellular solution and with microtubule collapse. The present study tests the hypothesis that limitation of nsPEF-induced Ca2+ influx and colloid osmotic cell swelling permits unabated lysosome translocation in exposed cells. The results indicate that the efforts used herein to preclude Ca2+ influx and colloid osmotic swelling following nsPEF exposure did not prevent attenuation of lysosome translocation. Intracellular lysosome movement is inhibited by nsPEF exposure(s) in the presence of PEG 300-containing solution or by 20 pulses of nsPEF in the presence of extracellular calcium. The only cases with no significant decreases in lysosome movement are the sham and exposure to a single nsPEF in Ca2+-free solution.

The study of living cells may require advanced imaging techniques to track weak and rapidly changing signals. Fundamental to this need is the recent advancement in camera technology. Two camera types, specifically sCMOS and EM-CCD, promise both high signal-to-noise and high speed (>100 fps), leaving researchers with a critical decision when determining the best technology for their application. In this article, we compare two cameras using a live-cell imaging test case in which small changes in cellular fluorescence must be rapidly detected with high spatial resolution. The EM-CCD maintained an advantage of being able to acquire discernible images with a lower number of photons due to its EM-enhancement. However, if high-resolution images at speeds approaching or exceeding 1000 fps are desired, the flexibility of the full-frame imaging capabilities of sCMOS is superior.

High-amplitude, MV/m, nanosecond pulsed electric fields (nsPEF) have been hypothesized to cause nanoporation of the plasma membrane. Phosphatidylserine (PS) externalization has been observed on the outer leaflet of the membrane shortly after nsPEF exposure, suggesting local structural changes in the membrane. In this study, we utilized fluorescently-tagged Annexin V to observe the externalization of PS on the plasma membrane of isolated Chinese Hamster Ovary (CHO) cells following exposure to nsPEF. A series of experiments were performed to determine the dosimetric trends of PS expression caused by nsPEF as a function of pulse duration, τ, delivered field strength, ED, and pulse number, n. To accurately estimate dose thresholds for cellular response, data were reduced to a set of binary responses and ED50s were estimated using Probit analysis. Probit analysis results revealed that PS externalization followed the non-linear trend of (τ*ED (2))(-1) for high amplitudes, but failed to predict low amplitude responses. A second set of experiments was performed to determine the nsPEF parameters necessary to cause observable calcium uptake, using cells preloaded with calcium green (CaGr), and membrane permeability, using FM1-43 dye. Calcium influx and FM1-43 uptake were found to always be observed at lower nsPEF exposure parameters compared to PS externalization. These findings suggest that multiple, higher amplitude and longer pulse exposures may generate pores of larger diameter enabling lateral diffusion of PS; whereas, smaller pores induced by fewer, lower amplitude and short pulse width exposures may only allow extracellular calcium and FM1-43 uptake.

ObjectivesHigher prevalence of suicidality has been reported in individuals with ASD. This study aimed to (1) Estimate the prevalence of suicidal ideation (SI) in epidemiologically-ascertained, population-based, samples of children with ASD or Autism Spectrum Screening Questionnaire (ASSQ) Screen Positivity (ASP); (2) Determine whether ASD/ASP is an independent risk factor for SI, controlling for known SI risk factors; and, (3) Develop an explanatory model for SI in children with ASD/ASP.MethodsParticipants came from three epidemiologically-ascertained samples of school-aged Korean children (n = 14,423; 3,702; 4,837). ASSQ ≥ 14 was the cutoff for ASP. A subsample (n = 86) was confirmed to have ASD. SI was based on parents' endorsement of items on the Behavioral Assessment System for Children-2-Parent Report Scale-Children. Logistic regressions were used to assess associations between SI and ASD/ASP, controlling for demographics, peer victimization, behavior problems, and depression. To develop an explanatory model for SI within ASD/ASP, the associations between SI and child characteristics (comorbid conditions, ASD symptoms, IQ, adaptive function) were tested.ResultsSI was higher in children with ASD (14%) and ASP (16.6-27.4%) than ASSQ Screen Negative (ASN) peers (3.4-6.9%). ASD/ASP was strongly predictive of SI (ORs: 2.87-5.67), after controlling for known SI risk factors compared to ASN. Within the ASD and ASP groups, anxiety was the strongest predictor of SI.ConclusionsSI prevalence was higher in non-clinical samples of children with ASD and ASP, relative to ASN peers. These results underscore the need for routine screening for SI in children with ASD and social difficulties, particularly those with high anxiety. HighlightsPopulation-based, epidemiologically-ascertained, school-aged childrenASD and ASP are independent risk factors for SI in school-aged childrenAnxiety is an independent risk factor for SI in children with ASD or ASP.

In this study, we determined the LD(50) (50% lethal dose) for cell death, and the ED(50) (50% of cell population staining positive) for propidium (Pr) iodide uptake, and phosphatidylserine (PS) externalization for several commonly studied cell lines (HeLa, Jurkat, U937, CHO-K1, and GH3) exposed to 10-ns electric pulses (EP). We found that the LD(50) varied substantially across the cell lines studied, increasing from 51 J/g for Jurkat to 1861 J/g for HeLa. PS externalized at doses equal or lower than that required for death in all cell lines ranging from 51 J/g in Jurkat, to 199 J/g in CHO-K1. Pr uptake occurred at doses lower than required for death in three of the cell lines: 656 J/g for CHO-K1, 634 J/g for HeLa, and 142 J/g for GH3. Both Jurkat and U937 had a LD(50) lower than the ED(50) for Pr uptake at 780 J/g and 1274 J/g, respectively. The mechanism responsible for these differences was explored by evaluating cell size, calcium concentration in the exposure medium, and effect of trypsin treatment prior to exposure. None of the studied parameters correlated with the observed results suggesting that cellular susceptibility to injury and death by 10-ns EP was largely determined by cell physiology. In contrast to previous studies, our findings suggest that permeabilization of internal membranes may not necessarily be responsible for cell death by 10-ns EP. Additionally, a mixture of Jurkat and HeLa cells was exposed to 10-ns EP at a dose of 280 J/g. Death was observed only in Jurkat cells suggesting that 10-ns EP may selectively kill cells within a heterogeneous tissue.

Lay abstractWhat is Already Known about This Subject: Genetics, (including de novo mutations), environmental factors (including toxic exposures), and their interactions impact autism spectrum disorder etiology. Paternal smoking is a candidate risk for autism spectrum disorder due to biological plausibility, high prevalence, and potential intervention.What This Study Adds: This original study and its replication confirms that paternal factors can substantially contribute to autism spectrum disorder risk for their offspring. It specifically indicates that paternal smoking both before and during pregnancy contributes significantly to autism spectrum disorder risk.Implications for practice, research, or policy: Smoking prevention, especially in pregnancy planning, may decrease autism spectrum disorder risk in offspring.

This study examined the effectiveness of a physical activity (PA) intervention among obese Hispanic children delivered by a free mobile phone game application (app) recommended by a pediatrician. A sample of 40 (age M=10.16[2.01] years) children participated in this pilot study. Pre- and posttest data were collected on participants' PA attitudes, intention, and objectively measured PA. The intervention was a game-based exercise prescription to engage in at least 20 minutes daily for seven days in moderate-to-vigorous PA (MVPA) delivered by their primary care pediatrician. The results showed a statistically significant decrease in sedentary time (SED) (t(26)=3.03, p=0.007, d=0.66) and an increase in moderate PA (MPA) (t(26)=3.19, p=0.005, d=-0.69), vigorous PA (VPA) (t(26)=-5.74, p<0.001, d=-1.25), and MVPA (t(26)=-9.09, p<0.001, d=-1.89). In addition, the study showed increase in PA attitudes (t(26)=-3.63, p<0.001, d=-1.10) and PA intention (t(20)=-3.13, p=0.001, d=-0.94) after the intervention. This study provides evidence that a mobile app gaming-based exercise prescription may help to engage obese Hispanic children in health enhancing PA.

Through this meta-analysis, we sought to examine the prevalence of, risks for, and factors associated with bullying involvement (victimization, perpetration, perpetration-victimization) among students with autism spectrum disorder (ASD). Additionally, we attempted to examine sources of variance in the prevalence and effect sizes of bullying in students with ASD across studies. Systematic database and literature review identified 34 relevant studies (31 for Western countries, three for Eastern countries). Pooled prevalence estimates for victimization, perpetration, and perpetration-victimization in general were 67%, 29%, and 14%, respectively. The risk of victimization in students with ASD was significantly higher than that in typically developing students and students with other disabilities. Further, deficits in social interaction and communication, externalizing symptoms, internalizing symptoms, and integrated inclusive school settings were related to higher victimization, and externalizing symptoms were related to higher perpetration. Finally, moderation analyses revealed significant variations in the pooled prevalences thereof depending on culture, age, school settings, and methodological quality and in the pooled effect sizes according to publication year and methodological quality. Our results highlight needs for bullying intervention for students with ASD, especially those who are younger, are in an inclusive school setting, and have higher social difficulties and externalizing/internalizing symptoms; for intensive research of bullying experiences among students with ASD in Eastern countries; and for efforts to improve the methodological quality of such research.

While a growing number of studies indicate associations between experiences of bullying and autism spectrum disorder (ASD), it is not clear what roles comorbid behavioral problems may play. We investigated the experiences of children with ASD as victims and/or perpetrators of bullying. Children with ASD epidemiologically ascertained participated in a cross-sectional study. Although children with ASD showed significantly increased risk for bullying involvement compared to community children, after controlling for comorbid psychopathology and other demographic factors, increased risks for being perpetrators or victim-perpetrators disappeared while risk for being bullied/teased continued to be significantly elevated. This finding will help guide medical, educational and community personnel to effectively identify children with ASD at risk for school bullying and develop interventions.