Publications by authors named "Nelson B"

2,411 Publications

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Cancer screenings during the COVID-19 pandemic: An analysis of public interest trends.

Curr Probl Cancer 2021 Jun 21:100766. Epub 2021 Jun 21.

Oklahoma State University Center for Health Sciences, College of Osteopathic Medicine, Department of Psychiatry and Behavioral Sciences, Tulsa, Oklahoma.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has impacted breast, colon, prostate, and lung cancer screenings in the U.S. by decreasing screening numbers.​We believe multiple types of cancer screenings may have been impacted during the pandemic as a result of cancellations of elective procedures and patient fear of seeking cancer screenings during a pandemic and that Google Trends may be a marker to estimate screening usage.

Methods: Google Trends (trends.google.com) was utilized to assess public interest in multiple cancer types. We then constructed a forecasting model to determine the expected search interest had the pandemic not occurred. We then compared our models to actual screening usage during the pandemic.

Results: Public interest in cancer screenings decreased precipitously at the onset of the COVID-19 pandemic. We found that the Google Trends estimated the decrease in mammogram usage 25.8% below the actual value. Similarly, Google Trends estimated the decrease in colon cancer screening usage 9.7% below the true value.

Discussion: We found the decrease in public interest in breast and colon cancer screenings slightly underestimated the actual screening usage numbers, suggesting Google Trends may be utilized as an indicator for human behavior regarding cancer screening, particularly with colon and breast cancer screenings. If the negative trend in cancer screening continues and missed screenings are not appropriately corrected for, socioeconomic and racial disparities in cancer diagnoses, morbidity, and mortality will widen.
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http://dx.doi.org/10.1016/j.currproblcancer.2021.100766DOI Listing
June 2021

A Submillimeter Continuous Variable Stiffness Catheter for Compliance Control.

Adv Sci (Weinh) 2021 Jul 17:e2101290. Epub 2021 Jul 17.

Institute of Robotics and Intelligent Systems, ETH Zurich, Zurich, CH-8092, Switzerland.

Minimally invasive robotic surgery often requires functional tools that can change their compliance to adapt to the environment and surgical needs. This paper proposes a submillimeter continuous variable stiffness catheter equipped with a phase-change alloy that has a high stiffness variation in its different states, allowing for rapid compliance control. Variable stiffness is achieved through a variable phase boundary in the alloy due to a controlled radial temperature gradient. This catheter can be safely navigated in its soft state and rigidified to the required stiffness during operation to apply a desired force at the tip. The maximal contact force that the catheter applies to tissue can be continuously modified by a factor of 400 (≈20 mN-8 N). The catheter is equipped with a magnet and a micro-gripper to perform a fully robotic ophthalmic minimally invasive surgery on an eye phantom by means of an electromagnetic navigation system.
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http://dx.doi.org/10.1002/advs.202101290DOI Listing
July 2021

Early Onset Neutropenia due to Rituximab Therapy in Mantle Cell Lymphoma: A Case Report.

J Hematol 2021 Jun 16;10(3):136-138. Epub 2021 Jun 16.

Department of Hematology & Oncology, MD Anderson Cancer Center, Houston, TX, USA.

Cases of late onset neutropenia (LON) after rituximab therapy have been documented, but few cases have been documented of early onset neutropenia (EON). We present a case report of a patient with mantle cell lymphoma who presented with EON, only 6 days after initiation of rituximab therapy, notable for the shortest duration to EON ever reported in literature. Throughout this paper, we explore the potential pathogenesis and incidence of EON with the help of our unique case.
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http://dx.doi.org/10.14740/jh814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256914PMC
June 2021

Bio-inspired Acousto-magnetic Microswarm Robots with Upstream Motility.

Nat Mach Intell 2021 Feb 11;3(2):116-124. Epub 2021 Jan 11.

Institute of Robotics and Intelligent Systems (IRIS), ETH Zurich, Zurich, CH-8092, Switzerland.

The ability to propel against flows, i.e., to perform positive rheotaxis, can provide exciting opportunities for applications in targeted therapeutics and non-invasive surgery. To date, no biocompatible technologies exist for navigating microparticles upstream when they are in a background fluid flow. Inspired by many naturally- occurring microswimmers such as bacteria, spermatozoa, and plankton that utilize the non-slip boundary conditions of the wall to exhibit upstream propulsion, here, we report on the design and characterization of self-assembled microswarms that can execute upstream motility in a combination of external acoustic and magnetic fields. Both acoustic and magnetic fields are safe to humans, non-invasive, can penetrate deeply into the human body, and are well-developed in clinical settings. The combination of both fields can overcome the limitations encountered by single actuation methods. The design criteria of the acoustically-induced reaction force of the microswarms, which is needed to perform rolling-type motion, are discussed. We show quantitative agreement between experimental data and our model that captures the rolling behaviour. The upstream capability provides a design strategy for delivering small drug molecules to hard-to-reach sites and represents a fundamental step toward the realization of micro- and nanosystem-navigation against the blood flow.
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http://dx.doi.org/10.1038/s42256-020-00275-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611213PMC
February 2021

Immune checkpoint blockade in triple negative breast cancer influenced by B cells through myeloid-derived suppressor cells.

Commun Biol 2021 Jul 12;4(1):859. Epub 2021 Jul 12.

McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.

Triple negative breast cancer holds a dismal clinical outcome and as such, patients routinely undergo aggressive, highly toxic treatment regimens. Clinical trials for TNBC employing immune checkpoint blockade in combination with chemotherapy show modest prognostic benefit, but the percentage of patients that respond to treatment is low, and patients often succumb to relapsed disease. Here, we show that a combination immunotherapy platform utilizing low dose chemotherapy (FEC) combined with oncolytic virotherapy (oHSV-1) increases tumor-infiltrating lymphocytes, in otherwise immune-bare tumors, allowing 60% of mice to achieve durable tumor regression when treated with immune checkpoint blockade. Whole-tumor RNA sequencing of mice treated with FEC + oHSV-1 shows an upregulation of B cell receptor signaling pathways and depletion of B cells prior to the start of treatment in mice results in complete loss of therapeutic efficacy and expansion of myeloid-derived suppressor cells. Additionally, RNA sequencing data shows that FEC + oHSV-1 suppresses genes associated with myeloid-derived suppressor cells, a key population of cells that drive immune escape and mediate therapeutic resistance. These findings highlight the importance of tumor-infiltrating B cells as drivers of antitumor immunity and their potential role in the regulation of myeloid-derived suppressor cells.
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http://dx.doi.org/10.1038/s42003-021-02375-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275624PMC
July 2021

High-speed feedback control of an oscillating magnetic helicity injector using a graphics processing unit.

Rev Sci Instrum 2021 May;92(5):053530

CTFusion, Inc., Seattle, Washington 98121, USA.

A real-time control system has been developed to control the amplitude, phase, and offset of bulk plasma parameters inside an oscillating magnetic helicity injector. Control software running entirely on an Nvidia Tesla P40 graphical processing unit is able to receive digitizer inputs and send response patterns to a Pulse Width Modulation (PWM) controller with a minimum control loop period of 12.8 µs. With an input digitization rate of 10 MS/s, a three-parameter proportional integral differential controller is shown to be sufficient to inform the PWM controller to drive the desired oscillating plasma waveform with a frequency of 16.6 kHz that is located near the resonance of a coupled RLC circuit. In particular, the temporal phase of the injector waveform is held within 10° of the target value. Control is demonstrated over the toroidal modal structure of the imposed magnetic perturbations of the helicity injection system, allowing a new class of discharges to be studied.
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http://dx.doi.org/10.1063/5.0044805DOI Listing
May 2021

Embedded Microbubbles for Acoustic Manipulation of Single Cells and Microfluidic Applications.

Anal Chem 2021 Jul 6;93(28):9760-9770. Epub 2021 Jul 6.

Department of Mechanical and Process Engineering, ETH Zurich, Multi-Scale Robotics Lab, Institute of Robotics and Intelligent Systems, Tannenstrasse 3, 8092 Zurich, Switzerland.

Acoustically excited microstructures have demonstrated significant potential for small-scale biomedical applications by overcoming major microfluidic limitations. Recently, the application of oscillating microbubbles has demonstrated their superiority over acoustically excited solid structures due to their enhanced acoustic streaming at low input power. However, their limited temporal stability hinders their direct applicability for industrial or clinical purposes. Here, we introduce the embedded microbubble, a novel acoustofluidic design based on the combination of solid structures (poly(dimethylsiloxane)) and microbubbles (air-filled cavity) to combine the benefits of both approaches while minimizing their drawbacks. We investigate the influence of various design parameters and geometrical features through numerical simulations and experimentally evaluate their manipulation capabilities. Finally, we demonstrate the capabilities of our design for microfluidic applications by investigating its mixing performance as well as through the controlled rotational manipulation of individual HeLa cells.
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http://dx.doi.org/10.1021/acs.analchem.1c01209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295982PMC
July 2021

Toxoplasma gondii, Herpesviridae and long-term risk of transition to first-episode psychosis in an ultra high-risk sample.

Schizophr Res 2021 Jul 2;233:24-30. Epub 2021 Jul 2.

Orygen, Parkville, Melbourne, Australia; Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.

Background: Ultra high-risk (UHR) criteria were introduced to identify people at imminent risk of developing psychosis. To improve prognostic accuracy, additional clinical and biological risk factors have been researched. Associations between psychotic disorders and infections with Toxoplasma gondii and Herpesviridae have been found. It is unknown if exposure to those pathogens increases the risk of transition to psychosis in UHR cohorts.

Methods: We conducted a long-term follow-up of 96 people meeting UHR criteria, previously seen at the Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service in Melbourne, Australia. Transition to psychosis was assessed using the Comprehensive Assessment of the At-Risk Mental State (CAARMS) and state public mental health records. The relationship between IgG antibodies to Herpesviridae (HSV-1, HSV-2, CMV, EBV, VZV) and Toxoplasma gondii and risk for transition was examined with Cox regression models.

Results: Mean follow-up duration was 6.46 (±3.65) years. Participants who transitioned to psychosis (n = 14) had significantly higher antibody titers for Toxoplasma gondii compared to those who did not develop psychosis (p = 0.03). After adjusting for age, gender and year of baseline assessment, seropositivity for Toxoplasma gondii was associated with a 3.6-fold increase in transition hazard in multivariate Cox regression models (HR = 3.6; p = 0.036). No significant association was found between serostatus for Herpesviridae and risk of transition.

Conclusions: Exposure to Toxoplasma gondii may contribute to the manifestation of positive psychotic symptoms and increase the risk of transitioning to psychosis in UHR individuals.
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http://dx.doi.org/10.1016/j.schres.2021.06.012DOI Listing
July 2021

Macrolactin A as a Novel Inhibitory Agent for SARS-CoV-2 M: Bioinformatics Approach.

Appl Biochem Biotechnol 2021 Jul 1. Epub 2021 Jul 1.

Research Divisions, Association for Biodiversity Conservation and Research, Balasore, Odisha, 756001, India.

COVID-19 is a disease that puts most of the world on lockdown and the search for therapeutic drugs is still ongoing. Therefore, this study used in silico screening to identify natural bioactive compounds from fruits, herbaceous plants, and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2 (PDB: 6LU7). We have used extensive screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME, molecular dynamics (MD) simulation, and MM/GBSA. A total of 17 compounds were shortlisted using Lipinski's rule in which 5 compounds showed significant predicted antiviral activity values. Among these 5, only 2 compounds, Macrolactin A and Stachyflin, showed good binding energy of -9.22 and -8.00 kcal/mol, respectively, within the binding pocket of the M catalytic residues (HIS 41 and CYS 145). These two compounds were further analyzed to determine their ADME properties. The ADME evaluation of these 2 compounds suggested that they could be effective in developing therapeutic drugs to be used in clinical trials. MD simulations showed that protein-ligand complexes of Macrolactin A and Stachyflin with the target receptor (6LU7) were stable for 100 nanoseconds. The MM/GBSA calculations of M-Macrolactin A complex indicated higher binding free energy (-42.58 ± 6.35 kcal/mol). Dynamic cross-correlation matrix (DCCM) and principal component analysis (PCA) on the residual movement in the MD trajectories further confirmed the stability of Macrolactin A bound state with 6LU7. In conclusion, this study showed that marine natural compound Macrolactin A could be an effective therapeutic inhibitor against SARS-CoV-2 protease (6LU7). Additional in vitro and in vivo validations are strongly needed to determine the efficacy and therapeutic dose of Macrolactin A in biological systems.
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http://dx.doi.org/10.1007/s12010-021-03608-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248955PMC
July 2021

Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans.

Sci Rep 2021 Jun 30;11(1):13619. Epub 2021 Jun 30.

Department of Microbiology and Molecular Genetics, Oklahoma State University, 307 Life Science East, Stillwater, OK, 74078, USA.

Cryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.
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http://dx.doi.org/10.1038/s41598-021-92991-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245489PMC
June 2021

Cannabidiol for at risk for psychosis youth: A randomized controlled trial.

Early Interv Psychiatry 2021 Jun 30. Epub 2021 Jun 30.

Orygen, Melbourne, Australia.

Background: No biological treatment has been firmly established for the at-risk stage of psychotic disorder. In this study we aim to test if subthreshold psychotic symptoms can be effectively treated with cannabidiol (CBD), a non-psychoactive compound of the plant Cannabis sativa. The question has taken on increased importance in the wake of evidence questioning both the need and efficacy of specific pharmacological interventions in the ultra-high risk (UHR) for psychosis group.

Methods: Three-arm randomized controlled trial of 405 patients (135 per arm) aged 12-25 years who meet UHR for psychosis criteria. The study includes a 6-week lead-in phase during which 10% of UHR individuals are expected to experience symptom remission. Participants will receive CBD (per oral) at doses 600 or 1000 mg per day (fixed schedule) for 12 weeks. Participants in the third arm of the trial will receive matching placebo capsules. Primary outcome is severity of positive psychotic symptoms as measured by the Comprehensive Assessment of At-Risk Mental States at 12 weeks. We hypothesize that CBD will be significantly more effective than placebo in improving positive psychotic symptoms in UHR patients. All participants will also be followed up 6 months post baseline to evaluate if treatment effects are sustained.

Conclusion: This paper reports on the rationale and protocol of the Cannabidiol for At Risk for psychosis Youth (CanARY) study. This study will test CBD for the first time in the UHR phase of psychotic disorder.
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http://dx.doi.org/10.1111/eip.13182DOI Listing
June 2021

Concurrent and prospective associations between fitbit wearable-derived RDoC arousal and regulatory constructs and adolescent internalizing symptoms.

J Child Psychol Psychiatry 2021 Jun 29. Epub 2021 Jun 29.

Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Background: Adolescence is characterized by alterations in biobehavioral functioning, during which individuals are at heightened risk for onset of psychopathology, particularly internalizing disorders. Researchers have proposed using digital technologies to index daily biobehavioral functioning, yet there is a dearth of research examining how wearable metrics are associated with mental health.

Methods: We preregistered analyses using the Adolescent Brain Cognitive Development Study dataset using wearable data collection in 5,686 adolescents (123,862 person-days or 2,972,688 person-hours) to determine whether wearable indices of resting heart rate (RHR), step count, and sleep duration and variability in these measures were cross-sectionally associated with internalizing symptomatology. All models were also run controlling for age, sex, body mass index, socioeconomic status, and race. We then performed prospective analyses on a subset of this sample (n = 143) across 25 months that had Fitbit data available at baseline and follow-up in order to explore directionality of effects.

Results: Cross-sectional analyses revealed a small, yet significant, effect size (R  = .053) that higher RHR, lower step count and step count variability, and greater variability in sleep duration were associated with greater internalizing symptoms. Cross-lagged panel model analysis revealed that there were no prospective associations between wearable variables and internalizing symptoms (partial R  = .026), but greater internalizing symptoms and higher RHR predicted lower step count 25 months later (partial R  = .010), while higher RHR also predicted lower step count variability 25 months later (partial R  = .008).

Conclusions: Findings indicate that wearable indices concurrently associate with internalizing symptoms during early adolescence, while a larger sample size is likely required to accurately assess prospective or directional effects between wearable indices and mental health. Future research should capitalize on the temporal resolution provided by wearable devices to determine the intensive longitudinal relations between biobehavioral risk factors and acute changes in mental health.
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http://dx.doi.org/10.1111/jcpp.13471DOI Listing
June 2021

Neuroticism and respiratory sinus arrhythmia predict increased internalizing symptoms during the COVID-19 pandemic.

Pers Individ Dif 2021 Nov 19;182:111053. Epub 2021 Jun 19.

Department of Psychology, Stony Brook University, United States.

The coronavirus (COVID-19) pandemic has impacted young adults across a number of different domains. It is critical to establish the degree to which the COVID-19 pandemic has affected mental health and identify predictors of poor outcomes. Neuroticism and (low) respiratory sinus arrhythmia (RSA) are risk factors of internalizing disorders that might predict increased psychopathology symptoms. The present study included 222 undergraduate students from [name removed] in Long Island, NY. Before the COVID-19 pandemic, participants completed self-report measures of neuroticism and internalizing symptoms and an electrocardiogram. Between April 15th to May 30th, 2020, participants again completed the measure of internalizing symptoms and a questionnaire about COVID-19 experiences. The COVID-19 pandemic was associated with increased distress, fear/obsessions, and (low) positive mood symptoms. There was a Neuroticism x RSA interaction in relation to distress symptoms, such that greater pre-COVID-19 neuroticism was associated with increased distress symptoms, but only in the context of low RSA. These findings suggest the COVID-19 pandemic has contributed to increased internalizing symptoms in young adults, and individuals with specific personality and autonomic risk factors may be at heightened risk for developing psychopathology.
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http://dx.doi.org/10.1016/j.paid.2021.111053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213985PMC
November 2021

Functional Connectivity in Antipsychotic-Treated and Antipsychotic-Naive Patients With First-Episode Psychosis and Low Risk of Self-harm or Aggression: A Secondary Analysis of a Randomized Clinical Trial.

JAMA Psychiatry 2021 Jun 23. Epub 2021 Jun 23.

Turner Institute for Brain and Mental Health, Monash University School of Psychological Sciences, Clayton, Victoria, Australia.

Importance: Altered functional connectivity (FC) is a common finding in resting-state functional magnetic resonance imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotic treatment influences these disturbances, remains unknown.

Objective: To investigate longitudinal FC changes in antipsychotic-naive and antipsychotic-treated patients with first-episode psychosis (FEP).

Design, Setting, And Participants: This secondary analysis of a triple-blind, randomized clinical trial was conducted over a 5-year recruitment period between April 2008 and December 2016 with 59 antipsychotic-naive patients with FEP receiving either a second-generation antipsychotic or a placebo pill over a treatment period of 6 months. Participants were required to have low suicidality and aggression, to have a duration of untreated psychosis of less than 6 months, and to be living in stable accommodations with social support. Both FEP groups received intensive psychosocial therapy. A healthy control group was also recruited. Participants completed rs-fMRI scans at baseline, 3 months, and 12 months. Data were analyzed from May 2019 to August 2020.

Interventions: Resting-state functional MRI was used to probe brain FC. Patients received either a second-generation antipsychotic or a matched placebo tablet. Both patient groups received a manualized psychosocial intervention.

Main Outcomes And Measures: The primary outcomes of this analysis were to investigate (1) FC differences between patients and controls at baseline; (2) FC changes in medicated and unmedicated patients between baseline and 3 months; and (3) associations between longitudinal FC changes and clinical outcomes. An additional aim was to investigate long-term FC changes at 12 months after baseline. These outcomes were not preregistered.

Results: Data were analyzed for 59 patients (antipsychotic medication plus psychosocial treatment: 28 [47.5%]; mean [SD] age, 19.5 [3.0] years; 15 men [53.6%]; placebo plus psychosocial treatment: 31 [52.5%]; mean [SD] age, 18.8 [2.7]; 16 men [51.6%]) and 27 control individuals (mean [SD] age, 21.9 [1.9] years). At baseline, patients showed widespread functional dysconnectivity compared with controls, with reductions predominantly affecting interactions between the default mode network, limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems; some of these changes correlated with improved clinical outcomes (canonical correlation analysis R = 0.901; familywise error-corrected P = .005). Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain.

Conclusions And Relevance: In this secondary analysis of a clinical trial, antipsychotic-naive patients with FEP showed widespread functional dysconnectivity at baseline, followed by an early normalization of default mode network and cortical limbic dysfunction in patients receiving placebo and psychosocial intervention. Antipsychotic exposure was associated with FC changes concentrated on thalamocortical networks.

Trial Registration: ACTRN12607000608460.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.1422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223142PMC
June 2021

Affective and Autonomic Reactivity During Parent-Child Interactions in Depressed and Non-Depressed Mothers and Their Adolescent Offspring.

Res Child Adolesc Psychopathol 2021 Jun 17. Epub 2021 Jun 17.

Department of Psychology, University of Oregon, Eugene, OR, USA.

Depression presents risks that are profound and intergenerational, yet research on the association of depression with the physiological processes that might be associated with impaired mental and physical health has only recently been contextualized within the family environment. Participants in this multi-method case-control study were 180 mother-adolescent dyads (50% mothers with a history of depression treatment and current depressive symptoms). In order to examine the association between maternal depression and affective and autonomic reactivity amongst these mothers and their adolescent offspring we collected self-reported measures of positive and negative affect, as well as measures of cardiovascular and electrodermal autonomic activity, during mother-adolescent interaction tasks. Findings indicated that depressed mothers and their adolescent offspring exhibited greater self-reported negative affect reactivity during a problem-solving interaction and blunted (i.e., low) sympathetic activity as measured via skin conductance level across both interaction tasks. These effects remained significant after controlling for a range of potential covariates, including medication use, sex, age, adolescents own mental health symptoms, and behavior of the other interactant, along with correcting for multiple comparisons. Findings indicate that depressed mothers and their adolescent offspring both exhibit patterns of affect and physiology during interactions that are different from those of non-depressed mothers and their offspring, including increased negative affect reactivity during negative interactions and blunted sympathetic activity across both positive and negative interactions. These findings have potential implications for understanding the role of family processes in the intergenerational transmission of risk for depressive disorders.
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http://dx.doi.org/10.1007/s10802-021-00840-xDOI Listing
June 2021

Modelling the Impact of Robotics on Infectious Spread Among Healthcare Workers.

Front Robot AI 2021 25;8:652685. Epub 2021 May 25.

Department of Neurosurgery, Henan Provincial People's Hospital, Henan University People's Hospital, Henan University School of Medicine, Zhengzhou, China.

The Coronavirus disease 2019 (Covid-19) pandemic has brought the world to a standstill. Healthcare systems are critical to maintain during pandemics, however, providing service to sick patients has posed a hazard to frontline healthcare workers (HCW) and particularly those caring for elderly patients. Various approaches are investigated to improve safety for HCW and patients. One promising avenue is the use of robots. Here, we model infectious spread based on real spatio-temporal precise personal interactions from a geriatric unit and test different scenarios of robotic integration. We find a significant mitigation of contamination rates when robots specifically replace a moderate fraction of high-risk healthcare workers, who have a high number of contacts with patients and other HCW. While the impact of robotic integration is significant across a range of reproductive number R, the largest effect is seen when R is slightly above its critical value. Our analysis suggests that a moderate-sized robotic integration can represent an effective measure to significantly reduce the spread of pathogens with Covid-19 transmission characteristics in a small hospital unit.
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http://dx.doi.org/10.3389/frobt.2021.652685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185357PMC
May 2021

Osteochondritis Dissecans: Current Understanding of Epidemiology, Etiology, Management, and Outcomes.

J Bone Joint Surg Am 2021 Jun;103(12):1132-1151

Department of Orthopedic Surgery, University of Minnesota, Minneapolis, Minnesota.

: Osteochondritis dissecans occurs most frequently in the active pediatric and young adult populations, commonly affecting the knee, elbow, or ankle, and may lead to premature osteoarthritis.

: While generally considered an idiopathic phenomenon, various etiopathogenetic theories are being investigated, including local ischemia, aberrant endochondral ossification of the secondary subarticular physis, repetitive microtrauma, and genetic predisposition.

: Diagnosis is based on the history, physical examination, radiography, and advanced imaging, with elbow ultrasonography and novel magnetic resonance imaging protocols potentially enabling early detection and in-depth staging.

: Treatment largely depends on skeletal maturity and lesion stability, defined by the presence or absence of articular cartilage fracture and subchondral bone separation, as determined by imaging and arthroscopy, and is typically nonoperative for stable lesions in skeletally immature patients and operative for those who have had failure of conservative management or have unstable lesions.

: Clinical practice guidelines have been limited by a paucity of high-level evidence, but a multicenter effort is ongoing to develop accurate and reliable classification systems and multimodal decision-making algorithms with prognostic value.
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http://dx.doi.org/10.2106/JBJS.20.01399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272630PMC
June 2021

Characterization of Bacterial and Fungal Infections in Hospitalized Patients With Coronavirus Disease 2019 and Factors Associated With Health Care-Associated Infections.

Open Forum Infect Dis 2021 Jun 5;8(6):ofab201. Epub 2021 May 5.

Department of Medicine, Division of Infectious Diseases, Columbia University Irving Medical Center, New York, New York, USA.

Background: Patients hospitalized with coronavirus disease 2019 (COVID-19) are at increased risk of health care-associated infections (HAIs), especially with prolonged hospital stays. We sought to identify incidence, antimicrobial susceptibilities, and outcomes associated with bacterial/fungal secondary infections in a large cohort of patients with COVID-19.

Methods: We evaluated adult patients diagnosed with COVID-19 between 2 March and 31 May 2020 and hospitalized >24 hours. Data extracted from medical records included diagnoses, vital signs, laboratory results, microbiological data, and antibiotic use. Microbiologically confirmed bacterial and fungal pathogens from clinical cultures were evaluated to characterize community- and health care-associated infections, including describing temporal changes in predominant organisms on presentation and throughout hospitalization. Univariable and multivariable logistic regression analyses were performed to investigate risk factors for HAIs.

Results: A total of 3028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) patients with positive cultures met criteria for infection. Community-associated coinfections were identified in 183 (6%) patients, whereas HAIs occurred in 350 (12%) patients. Fifty-seven percent of HAIs were caused by gram-negative bacteria and 19% by fungi. Antibiotic resistance increased with longer hospital stays, with incremental increases in the proportion of vancomycin resistance among enterococci and ceftriaxone and carbapenem resistance among Enterobacterales. Intensive care unit stay, invasive mechanical ventilation, and steroids were associated with HAIs.

Conclusions: HAIs occur in a small proportion of patients hospitalized with COVID-19 and are most often caused by gram-negative and fungal pathogens. Antibiotic resistance is more prevalent with prolonged hospital stays. Antimicrobial stewardship is imperative in this population to minimize unnecessary broad-spectrum antibiotic use.
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http://dx.doi.org/10.1093/ofid/ofab201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135866PMC
June 2021

Emphysematous Cystitis.

Mayo Clin Proc 2021 06;96(6):1393

Division of Hospital Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1016/j.mayocp.2021.03.007DOI Listing
June 2021

Correction to: Systematic review of prospective studies focused on regionalization of care in surgical oncology.

Updates Surg 2021 Jun 3. Epub 2021 Jun 3.

Department of Surgery, Weill Cornell Medical College, New York, NY, USA.

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http://dx.doi.org/10.1007/s13304-021-01107-2DOI Listing
June 2021

Reduced Etch Lag and High Aspect Ratios by Deep Reactive Ion Etching (DRIE).

Micromachines (Basel) 2021 May 10;12(5). Epub 2021 May 10.

Department of Mechanical and Process Engineering, Institute for Mechanical Systems, 8092 Zurich, Switzerland.

Deep reactive ion etching (DRIE) with the Bosch process is one of the key procedures used to manufacture micron-sized structures for MEMS and microfluidic applications in silicon and, hence, of increasing importance for miniaturisation in biomedical research. While guaranteeing high aspect ratio structures and providing high design flexibility, the etching procedure suffers from reactive ion etching lag and often relies on complex oxide masks to enable deep etching. The reactive ion etching lag, leading to reduced etch depths for features exceeding an aspect ratio of 1:1, typically causes a height difference of above 10% for structures with aspect ratios ranging from 2.5:1 to 10:1, and, therefore, can significantly influence subsequent device functionality. In this work, we introduce an optimised two-step Bosch process that reduces the etch lag to below 1.5%. Furthermore, we demonstrate an improved three-step Bosch process, allowing the fabrication of structures with 6 μm width at depths up to 180 μm while maintaining their stability.
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http://dx.doi.org/10.3390/mi12050542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150727PMC
May 2021

Relationship Between Moral Distress and Intent to Leave a Position Among Neonatal Intensive Care Nurses.

Adv Neonatal Care 2021 May 27. Epub 2021 May 27.

Division of Neonatology, Department of Pediatrics, Massachusetts General Hospital, Boston (Ms Hally and Drs Settle and Nelson); and School of Nursing, Endicott College, Boston (Ms Hally); and Harvard Medical School, Boston (Dr Nelson).

Background: The phenomenon of moral distress is prevalent in the literature, but little is known about the experiences of nurses working in the neonatal intensive care unit (NICU). In addition, a paucity of literature exists exploring the relationship between moral distress and intent to leave a position in NICU nurses.

Purpose: To explore the phenomenon of moral distress in NICU nurses using the Measure of Moral Distress for Health Care Professionals (MMD-HP) survey.

Methods: A cross-sectional, descriptive, correlational study was conducted nationally via an electronic survey distributed to NICU nurses who are members of National Association of Neonatal Nurses (NANN). Participants were asked to electronically complete the MMD-HP survey between March 27 and April 8, 2020.

Findings: A total of 75 NICU nurses completed the survey, and 65 surveys were included for data analysis. Five situations from the survey had a composite MMD-HP score of more than 400. Results indicated that 41.5% of the NICU nurses surveyed considered leaving a clinical position due to moral distress, and 23.1% of the nurses surveyed left a position due to moral distress.

Implications For Practice: NICU nurses experiencing high MMD-HP scores are more likely to leave a position. Further research is needed to develop strategies useful in mitigating moral distress in and prevent attrition of NICU nurses.

Implications For Research: Many NICU nurses experiencing high levels of moral distress have left positions or are considering leaving a clinical position. Longitudinal interventional studies are vital to understand, prevent, and address the root causes of moral distress experienced by NICU nurses.
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http://dx.doi.org/10.1097/ANC.0000000000000891DOI Listing
May 2021

Use of cone-beam computed tomography for advanced imaging of the equine patient.

Equine Vet J 2021 May 30. Epub 2021 May 30.

Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.

Access to volumetric imaging modalities, such as magnetic resonance imaging (MRI) and computed tomography (CT), has increased over the past decade and has revolutionised the way clinicians evaluate equine anatomy. More recent advancements have resulted in the development of multiple commercially available cone-beam CT (CBCT) scanners for equine use. CBCT scanners modify the traditional fan-shaped beam of ionising radiation into a three-dimensional pyramidal- or cone-shaped beam of radiation. This modification enables the scanner to acquire sufficient data to create diagnostic images of a region of interest after a single rotation of the gantry. The rapid acquisition of data and divergent X-ray beam causes some artifacts to be more prominent on CBCT images-as well as the unique cone-beam artifact-resulting in decreased contrast resolution. While the use of CT for evaluation of the equine musculoskeletal anatomy is not new, there is a paucity of literature and scientific studies on the capabilities of CBCT for equine imaging. CBCT units do not require a specialised table for imaging and in some cases are portable for imaging in the standing or anaesthetised patient. This review article summarises the basic physics of CT technology, including how CBCT imaging differs, and provides objective information about the strengths and limitations of this modality. Finally, potential future applications and techniques for imaging with CT which will need to be explored in order to fully consider the capabilities of CT imaging in the horse are discussed.
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http://dx.doi.org/10.1111/evj.13473DOI Listing
May 2021

Stress reactivity as a putative mechanism linking childhood trauma with clinical outcomes in individuals at ultra-high-risk for psychosis: Findings from the EU-GEI High Risk Study.

Epidemiol Psychiatr Sci 2021 May 28;30:e40. Epub 2021 May 28.

Department of Public Mental Health, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany.

Aims: Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high-risk (UHR) for psychosis.

Methods: Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N = 79 UHR individuals in the EU-GEI High Risk Study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up.

Results: The association of stress with positive (β = -0.14, p = 0.010) and negative affect (β = 0.11, p = 0.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β = 0.06, p = 0.019) and psychotic experiences (β = 0.05, p = 0.037) was greater in individuals exposed to high v. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B = 6.29, p = 0.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. indirect effect: B = -2.13, p = 0.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. indirect effect: B = 0.14, p = 0.506).

Conclusions: Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.
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http://dx.doi.org/10.1017/S2045796021000251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193966PMC
May 2021

Tiny robots make big advances.

Sci Robot 2021 Mar;6(52)

Peer Fischer is a Professor of Physical Chemistry, University of Stuttgart, and heads the Micro, Nano, and Molecular Systems Laboratory at the Max Planck Institute for Intelligent Systems, Stuttgart, Germany. Email:

This special issue showcases developments in microactuation, microparticle control, and micro/nanorobots for biomedicine.
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http://dx.doi.org/10.1126/scirobotics.abh3168DOI Listing
March 2021

Progress in robotics for combating infectious diseases.

Sci Robot 2021 03;6(52)

Institute of Medical Robotics, Shanghai Jiao Tong University, 200240 Shanghai, China.

The world was unprepared for the COVID-19 pandemic, and recovery is likely to be a long process. Robots have long been heralded to take on dangerous, dull, and dirty jobs, often in environments that are unsuitable for humans. Could robots be used to fight future pandemics? We review the fundamental requirements for robotics for infectious disease management and outline how robotic technologies can be used in different scenarios, including disease prevention and monitoring, clinical care, laboratory automation, logistics, and maintenance of socioeconomic activities. We also address some of the open challenges for developing advanced robots that are application oriented, reliable, safe, and rapidly deployable when needed. Last, we look at the ethical use of robots and call for globally sustained efforts in order for robots to be ready for future outbreaks.
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http://dx.doi.org/10.1126/scirobotics.abf1462DOI Listing
March 2021

Slab fractures of the third carpal bone involving both radial and intermediate facets and outcomes after surgical repair in racing Quarter Horses.

Equine Vet J 2021 May 25. Epub 2021 May 25.

Orthopaedic Research Center, C. Wayne McIlwraith Translational Medicine Institute, Colorado State University, Fort Collins, CO, USA.

Background: Characteristics and outcomes after surgical repair of third carpal bone (C3) slab fractures involving both radial and intermediate facets in racing Quarter Horses are unknown.

Objectives: To describe the pre- and intraoperative characteristics of C3 slab fractures of both radial and intermediate facets in Quarter Horses and to report on the long-term outcomes after internal fixation.

Study Design: Retrospective case series.

Methods: Case records were collected from racehorses with C3 slab fractures between 2008 and 2020. Inclusion criteria required arthroscopic-guided repair of C3 slab fractures involving both radial and intermediate facets in Quarter Horses. Routine C3 slab fractures (single facet), fractures in other breeds or those repaired with other techniques were excluded. Outcomes were obtained by standardised questionnaire. Data were presented as mean ± SD or as proportions with 95% confidence interval (CI).

Results: Of 22 Quarter Horses with C3 slab fractures involving both radial and intermediate facets, 91% (CI 79%-100%; n = 20) were collapsing and 91% (CI 79%-100%; n = 20) had avulsion of the medial palmar intercarpal ligament. Articular cartilage erosion and osteochondral fracture of the radial carpal bone was observed in 91% (CI 79%-100%; n = 20) and 41% (CI 20%-62%; n = 9) cases respectively. At 5.5 ± 3.9 years after surgery, 86% (CI 72%-100%; n = 19) were alive and used for breeding or retirement. Of 18 horses with follow-up >1 year, 39% (CI 16%-61%; n = 7) resumed some athletic activity.

Main Limitations: Cases were referred specifically for surgical repair and horses with fractures considered too severe for surgical intervention or euthanasia at owner request were not included. Questionnaire responses are susceptible to recall bias.

Conclusions: Horses with C3 slab fractures of both radial and intermediate facets that are repaired have a favourable prognosis for retirement, breeding and potentially low-level athletic activity.
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http://dx.doi.org/10.1111/evj.13468DOI Listing
May 2021

Nano-3D-Printed Photochromic Micro-Objects.

Small 2021 Jul 24;17(26):e2101337. Epub 2021 May 24.

Empa, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Biomimetic Membranes and Textiles, Lerchenfeldstrasse 5, St. Gallen, 9014, Switzerland.

Molecular photoswitches that can reversibly change color upon irradiation are promising materials for applications in molecular actuation and photoresponsive materials. However, the fabrication of photochromic devices is limited to conventional approaches such as mold casting and spin-coating, which cannot fabricate complex structures. Reported here is the first photoresist for direct laser writing of photochromic 3D micro-objects via two-photon polymerization. The integration of photochromism into thiol-ene photo-clickable resins enables rapid two-photon laser processing of highly complex microstructures and facile postmodification using a series of donor-acceptor Stenhouse adduct (DASA) photoswitches with different excitation wavelengths. The versatility of thiol-ene photo-click reactions allows fine-tuning of the network structure and physical properties as well as the type and concentration of DASA. When exposed to visible light, these microstructures exhibit excellent photoresponsiveness and undergo reversible color-changing via photoisomerization. It is demonstrated that the fluorescence variations of DASAs can be used as a reporter of photoswitching and thermal recovery, allowing the reading of DASA-containing sub-micrometric structures in 3D. This work delivers a new approach for custom microfabrication of 3D photochromic objects with molecularly engineered color and responsiveness.
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http://dx.doi.org/10.1002/smll.202101337DOI Listing
July 2021
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