The recent SARS-CoV-2 pandemic underscores the need for rapid and accurate prediction of clinical thrombotic events. Here, we developed nanoengineered multichannel immunosensors for rapid detection of circulating biomarkers associated with thrombosis, including C-reactive protein (CRP), calprotectin, soluble platelet selectin (sP-selectin), and D-dimer. We fabricated the immunosensors using fiber laser engraving of carbon nanotubes and CO laser cutting of microfluidic channels, along with the electrochemical deposition of gold nanoparticles to conjugate with biomarker-specific aptamers and antibody.
View Article and Find Full Text PDFCRISPR-Cas systems confer adaptive immunity to their prokaryotic hosts through the process of adaptation, where sequences are captured from foreign nucleic acids and integrated as spacers in the CRISPR array, and thereby enable crRNA-guided interference against new threats. While the Cas1-2 integrase is critical for adaptation, it is absent from many CRISPR-Cas loci, rendering the mechanism of spacer acquisition unclear for these systems. Here we show that the RNA-targeting type VI-A CRISPR system of acquires spacers from DNA substrates through the action of a promiscuous Cas1-2 integrase encoded by a co-occurring type II-C system, in a transcription-independent manner.
View Article and Find Full Text PDFLight-sheet fluorescence microscopy (LSFM) introduces fast scanning of biological phenomena with deep photon penetration and minimal phototoxicity. This advancement represents a significant shift in 3-D imaging of large-scale biological tissues and 4-D (space + time) imaging of small live animals. The large data associated with LSFM requires efficient imaging acquisition and analysis with the use of artificial intelligence (AI)/machine learning (ML) algorithms.
View Article and Find Full Text PDFIn this prospective observational cohort study, we provide preliminary findings from a same-day multidisciplinary fast-tracked normal pressure hydrocephalus (NPH) clinic; incorporating the expertise of movement disorders neurologists, emphasizing the clinical characteristics, consensus classification, and management of patients referred for suspected NPH. We evaluated 111 patients (male/female: 67/44) from April 2022 to May 2023. Based on the multidisciplinary team consensus, 52 (46.
View Article and Find Full Text PDFImportance: Although older adults may use potentially driver-impairing (PDI) medications that can produce psychomotor impairment, little is known about changes to PDI medication use among older adults from the time before to the time after a motor vehicle crash (MVC).
Objective: To quantify use of and changes in PDI medications among older adults before and after an MVC.
Design, Setting, And Participants: This cohort study used linked Medicare claims and police-reported MVC data on 154 096 person-crashes among 121 846 older drivers.
Objectives: Neurocritically ill patients are at high risk for developing delirium, which can worsen the long-term outcomes of this vulnerable population. However, existing delirium assessment tools do not account for neurologic deficits that often interfere with conventional testing and are therefore unreliable in neurocritically ill patients. We aimed to determine the accuracy and predictive validity of the Fluctuating Mental Status Evaluation (FMSE), a novel delirium screening tool developed specifically for neurocritically ill patients.
View Article and Find Full Text PDFProkaryotic CRISPR-Cas immunity is subverted by anti-CRISPRs (Acrs), which inhibit Cas protein activities when expressed during the phage lytic cycle or from resident prophages or plasmids. Acrs often bind to specific cognate Cas proteins, and hence inhibition is typically limited to a single CRISPR-Cas subtype. Furthermore, although acr genes are frequently organized together in phage-associated gene clusters, how such inhibitors initially evolve has remained unclear.
View Article and Find Full Text PDFBackground: Administrative healthcare databases, such as Medicare, are increasingly used to identify groups at risk of a crash. However, they only contain information on crash-related injuries, not all crashes. If the driver characteristics associated with crash and crash-related injury differ, conflating the two may result in ineffective or imprecise policy interventions.
View Article and Find Full Text PDFBacteria have evolved anti-viral defenses, but the mechanisms of sensing and stopping infection are still under investigation. In this issue of Cell Host & Microbe, Mets, Kurata, Ernits et al. describe how direct sensing of a phage protein by a bacterial toxin-antitoxin-associated chaperone unleashes toxin activity to prevent infection.
View Article and Find Full Text PDFNon-benzodiazepine hypnotics ( "Z-drugs") are prescribed for insomnia, but might increase risk of motor vehicle crash (MVC) among older adults through prolonged drowsiness and delayed reaction times. We estimated the effect of initiating Z-drug treatment on the 12-week risk of MVC in a sequential target trial emulation. After linking New Jersey driver licensing and police-reported MVC data to Medicare claims, we emulated a new target trial each week (July 1, 2007 - October 7, 2017) in which Medicare fee-for-service beneficiaries were classified as Z-drug-treated or untreated at baseline and followed for an MVC.
View Article and Find Full Text PDFEarly-stage nonalcoholic fatty liver disease (NAFLD) is a silent condition, with most cases going undiagnosed, potentially progressing to liver cirrhosis and cancer. A non-invasive and cost-effective detection method for early-stage NAFLD detection is a public health priority but challenging. In this study, an adhesive, soft on-skin sensor with low electrode-skin contact impedance for early-stage NAFLD detection is fabricated.
View Article and Find Full Text PDFCell Reports speaks with Seth S. Margolis and Eric Villalón Landeros about their scientific journeys, experiences, and interests that have led to their recent work in our journal, which demonstrates a role for the neuronal membrane proteasome in modulating the activity of sensory neurons.
View Article and Find Full Text PDFBackground: Anticholinergic (AC) and sedative medications are a risk factor for cognitive impairment. This study sought to characterize AC and sedative use in older patients seen for outpatient neuropsychological evaluation and evaluate their associations with different cognitive domains. We hypothesized that AC and sedative use would be associated with worse attention/processing speed (AP), executive functioning (EF), and memory.
View Article and Find Full Text PDFProteasomes are critical for peripheral nervous system (PNS) function. Here, we investigate mammalian PNS proteasomes and reveal the presence of the neuronal membrane proteasome (NMP). We show that specific inhibition of the NMP on distal nerve fibers innervating the mouse hind paw leads to reduction in mechanical and pain sensitivity.
View Article and Find Full Text PDFMedication management errors are suspected to be prevalent among older adults with mild cognitive impairment (MCI). This study examined types of simulated medication-taking errors in cognitively normal older adults (CN; = 131), single domain amnestic MCI (sdMCI, = 91), and multi-domain MCI (mdMCI, = 44). Errors were measured using the medication management ability assessment (MMAA).
View Article and Find Full Text PDFArch Clin Neuropsychol
October 2024
Objective: Compensatory strategies can improve performance of instrumental activities of daily living in people with cognitive impairment. This study investigated patient interest in compensatory strategy interventions and preference for various intervention formats.
Methods: Semi-structured qualitative interviews with 38 older adults with cognitive impairment queried motivation to improve strategy use and interest in intervention formats/delivery methods.
Uncapped free 20S proteasomes are abundant and active in cells, and yet their degraded intracellular protein substrates have remained underexplored. In their recent study, Sharon and colleagues (Pepelnjak et al, 2024) developed an advanced proteomics method (PiP-MS) to comprehensively explore 20S proteasome substrates in the human proteome.
View Article and Find Full Text PDFPrevious research has found only a small, inconsistent association between hedonic consumption and subjective well-being, often attributed to individuals adapting to the happiness gains from their purchases. Given that diverse experiences can reduce or avert hedonic adaptation, we hypothesized that variety in hedonic spending would be associated with greater well-being. This hypothesis was tested in four studies (total N = 2,920), using both self-reported and objective bank-reported spending data.
View Article and Find Full Text PDFThe neuronal membrane proteasome (NMP) degrades intracellular proteins into peptides that are released directly into the extracellular space, whereby they stimulate neurons to promote signaling mechanisms that remain unknown. Here, we demonstrate that neuronal stimulation promotes NMP activity and, subsequently, enhanced production of NMP peptides. We show that these neuronal activity-dependent NMP peptides can rapidly promote N-methyl-D-aspartate receptor (NMDAR)-dependent calcium influx in neurons.
View Article and Find Full Text PDFBackground: Medications are one of the most easily modifiable risk factors for motor vehicle crashes (MVCs) among older adults, yet limited information exists on how the use of potentially driver-impairing (PDI) medications changes following an MVC. Therefore, we examined the number and types of PDI medication classes dispensed before and after an MVC.
Methods: This observational study included Medicare fee-for-service beneficiaries aged ≥67 years who were involved in a police-reported MVC in New Jersey as a driver between 2008 and 2017.
Background: Delirium is an acute cognitive disturbance frequently characterized by abnormal psychomotor activity and sleep-wake cycle disruption. However, the degree to which delirium affects activity patterns in the acute period after stroke is unclear. We aimed to examine these patterns in a cohort of patients with intracerebral hemorrhage (ICH).
View Article and Find Full Text PDFMacrophages employ an array of pattern recognition receptors to detect and eliminate intracellular pathogens that access the cytosol. The cytosolic carbohydrate sensors Galectin-3, -8, and -9 (Gal-3, Gal-8, and Gal-9) recognize damaged pathogen-containing phagosomes, and Gal-3 and Gal-8 are reported to restrict bacterial growth via autophagy in cultured cells. However, the contribution of these galectins to host resistance during bacterial infection in vivo remains unclear.
View Article and Find Full Text PDFAm J Phys Med Rehabil
February 2024
Objective: The study aims to determine whether Physical Medicine & Rehabilitation physicians offer naloxone per the Centers for Disease Control and Prevention Guidelines to patients at the highest risk of complications from opioid treatment and whether there is a difference between inpatient and outpatient naloxone prescribing.
Design: A retrospective chart review on 389 adults (outpatient n = 166; inpatient n = 223) from May 4 to May 31, 2022, at an academic rehabilitation hospital. Prescribed medications and comorbidities were evaluated to determine whether Centers for Disease Control and Prevention criteria for offering naloxone were met and whether naloxone was offered.