Characterizing a Silver Nanoparticle-Based Electrochemical Biosensor for Shiga Toxin Detection.

Shiga toxins (1, 2) regularly cause outbreaks and food recalls and pose a significant health risk to the infected population. Therefore, new reliable tools are needed to rapidly detect Shiga toxin cost-effectively in food, water, and wastewater before human consumption. Enzyme immunoassay and polymerase chain reaction approaches are the gold standard detection methods for the Shiga toxin. However, these methods require expensive instruments along with expensive reagents, which makes them hard to convert into point-of-use and low-cost systems. This study introduces an electrochemical biosensing method that utilizes silver nanoparticles (AgNPs) as electrochemical tags and commercially available low-cost screen-printed carbon electrodes for detection. This study introduces the modification of reference electrodes on commercially available screen-printed carbon electrodes to detect AgNPs dissolved in nitric acid. This biosensor achieved a 2 ng/mL lowest measured concentration for Shiga toxin-1 in less than 3 h. These biosensor results also showed that the AgNP-based sensor has better linearity (for graph between peak current vs concentration) and lower standard deviation compared to gold nanoparticles (AuNP)-based electrochemical biosensors.

A comparative cohort study of gastrointestinal oncology patients: Impact of a shift to telehealth on delivery of interprofessional cancer care.

Early studies of oncology visits performed via telehealth demonstrate patient and provider satisfaction; however, understanding of the impact of telehealth on clinic workflows is limited. The incorporation of telehealth visits into an interprofessional model of oncology care was evaluated to assess for changes in care delivery and patient engagement. New patients with a gastrointestinal cancer diagnosis who were actively undergoing treatment and followed for at least three months were divided into two cohorts based on telehealth utilization. Individual patient charts were reviewed by touchpoint, consisting of in-person visits, telehealth visits, phone calls, and patient portal messages. A total of 28 patient charts were analyzed, 11 pre-telehealth conventional care patients, and 17 telehealth patients. Telehealth cohort patients demonstrated an increased average number of total touchpoints when compared to the pre-telehealth cohort (p-value = 0.008) and had an increased number of patient portal and phone call touchpoints (p-value = 0.00 and 0.002). Telehealth provided more interactions between patients and providers demonstrating increased connectivity between a patient and their care team throughout their complex cancer journey. Clinic workflows may need to adjust to account for the increased demand of unscheduled patient interactions.

Three-Dimensional Lesion Phenotyping and Physiologic Characterization Inform Remyelination Ability in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) clinical management is based upon lesion characterization from 2-dimensional (2D) magnetic resonance imaging (MRI) views. Such views fail to convey the lesion-phenotype (ie, shape and surface texture) complexity, underlying metabolic alterations, and remyelination potential. We utilized a 3-dimensional (3D) lesion phenotyping approach coupled with imaging to study physiologic profiles within and around MS lesions and their impacts on lesion phenotypes. METHODS: Lesions were identified in 3T T2 -FLAIR images and segmented using geodesic active contouring. A calibrated fMRI sequence permitted measurement of cerebral blood flow (CBF), blood-oxygen-level-dependent signal (BOLD), and cerebral metabolic rate of oxygen (CMRO2 ). These metrics were measured within lesions and surrounding tissue in concentric layers exact to the 3D-lesion shape. BOLD slope was calculated as BOLD changes from a lesion to its surrounding perimeters. White matter integrity was measured using diffusion kurtosis imaging. Associations between these metrics and 3D-lesion phenotypes were studied. RESULTS: One hundred nine lesions from 23 MS patients were analyzed. We identified a noninvasive biomarker, BOLD slope, to metabolically characterize lesions. Positive BOLD slope lesions were metabolically active with higher CMRO2 and CBF compared to negative BOLD slope or inactive lesions. Metabolically active lesions with more intact white matter integrity had more symmetrical shapes and more complex surface textures compared to inactive lesions with less intact white matter integrity. CONCLUSION: The association of lesion phenotypes with their metabolic signatures suggests the prospect for translation of such data to clinical management by providing information related to metabolic activity, lesion age, and risk for disease reactivation and self-repair. Our findings also provide a platform for disease surveillance and outcome quantification involving myelin repair therapeutics.

Post-gadolinium 3-dimensional spatial, surface, and structural characteristics of glioblastomas differentiate pseudoprogression from true tumor progression.

PURPOSE: Pseudoprogression is often indistinguishable from true tumor progression on conventional 2-dimensional (2D) MRI in glioblastoma multiforme (GBM) patients. The aim of this study was to determine the association between post-gadolinium 3-dimensional (3D) characteristics and clinical state in GBM patients. METHODS: Standardized 3D brain MRI studies were performed, and contrast enhancing portions of each tumor were segmented and analyzed, blinded to clinical state, using principal component analysis (PCA), medial axis transformation (MAT), and coverage analysis. Associations between the 3D characteristics of the post-gadolinium enhanced regions and the clinical status of patients were performed. RESULTS: A total of 15 GBM patients [male: 11 (73%); median age (range): 62 years (36-72)] with a median disease duration of 6 months (range 2-24 months) were studied cross-sectionally with 6 (40%) patients identified with tumor progression. Post-gadolinium features corresponding to the group with progressive disease exhibited a more spherical and symmetric shape relative to their stable counterparts (p = 0.005). The predictive value of a more uniformly full post-gadolinium enhanced shell to clinical progression was determined with a sensitivity of 66.7% (95% CI 29.9-92.5), specificity of 100% (54.1-100), and PPV of 100% (p = 0.028, 2-tailed Fisher's exact test). There did not appear to be an association between the thickness of the contrast enhanced shell to clinical state. CONCLUSIONS: The application of 3D technology with post-gadolinium imaging data may inform healthcare providers with new insights into disease states based on spatial, surface, and structural patterns.

Precision medicine for multiple sclerosis promotes preventative medicine.

Multiple sclerosis (MS) is a chronic, lifelong disease, currently without a cure that is responsible for significant neurological injury in young adults. Precision medicine for MS aims to provide a more exacting and refined approach toward management by providing recommendations based on disease subtype, clinical status, existing radiological data, para-clinical data, and other biological markers. To achieve better outcomes, the three stages of care-diagnosis, treatment, and management-should be optimized. However, as the temporal profile of disease behavior is highly variable in MS, and unlike outcomes from other chronic conditions (i.e., hypertension, diabetes mellitus, etc.), should precision medicine for MS be one that focuses more on disease prevention and lifestyle modifications beyond recommendations for the use of disease-modifying therapies? As scientific advancements continue within the field of neuroimmunology, and until reliable biomarkers that predict disease outcomes are available, success may be better achieved by focusing on modifiable factors to reduce future disability.

Multiple Sclerosis in the Contemporary Age: Understanding the Millennial Patient with Multiple Sclerosis to Create Next-Generation Care.

The average age of onset of multiple sclerosis (MS) is between 20 and 40 years of age. Therefore, most new patients diagnosed with MS within the next 10 to 15 years will be from the millennial generation, representing those born between 1982 and 2000. Certain preferences and trends of this contemporary generation will present new challenges to the MS physician and effective MS care. By first understanding these challenges, relevant and successful solutions can be created to craft a system of care that best benefits the millennial patient with MS.

Function and regulation of tau conformations in the development and treatment of traumatic brain injury and neurodegeneration.

One of the two common hallmark lesions of Alzheimer's disease (AD) brains is neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau protein (p-tau). NFTs are also a defining feature of other neurodegenerative disorders and have recently been identified in the brains of patients suffering from chronic traumatic encephalopathy (CTE). However, NFTs are not normally observed in traumatic brain injury (TBI) until months or years after injury. This raises the question of whether NFTs are a cause or a consequence of long-term neurodegeneration following TBI. Two conformations of phosphorylated tau, cis p-tau and trans p-tau, which are regulated by the peptidyl-prolyl isomerase Pin1, have been previously identified. By generating a polyclonal and monoclonal antibody (Ab) pair capable of distinguishing between cis and trans isoforms of p-tau (cis p-tau and trans p-tau, respectively), cis p-tau was identified as a precursor of tau pathology and an early driver of neurodegeneration in AD, TBI and CTE. Histological studies shows the appearance of robust cis p-tau in the early stages of human mild cognitive impairment (MCI), AD and CTE brains, as well as after sport- and military-related TBI. Notably, cis p-tau appears within hours after closed head injury and long before other known pathogenic p-tau conformations including oligomers, pre-fibrillary tangles and NFTs. Importantly, cis p-tau monoclonal antibody treatment not only eliminates cis p-tau induction and tau pathology, but also restores many neuropathological and functional outcome in TBI mouse models. Thus, cis p-tau is an early driver of tau pathology in TBI and CTE and detection of cis p-tau in human bodily fluids could potentially provide new diagnostic and prognostic tools. Furthermore, humanization of the cis p-tau antibody could ultimately be developed as a new treatment for AD, TBI and CTE.

A phylogenomic analysis of turtles.

Molecular analyses of turtle relationships have overturned prevailing morphological hypotheses and prompted the development of a new taxonomy. Here we provide the first genome-scale analysis of turtle phylogeny. We sequenced 2381 ultraconserved element (UCE) loci representing a total of 1,718,154bp of aligned sequence. Our sampling includes 32 turtle taxa representing all 14 recognized turtle families and an additional six outgroups. Maximum likelihood, Bayesian, and species tree methods produce a single resolved phylogeny. This robust phylogeny shows that proposed phylogenetic names correspond to well-supported clades, and this topology is more consistent with the temporal appearance of clades and paleobiogeography. Future studies of turtle phylogeny using fossil turtles should use this topology as a scaffold for their morphological phylogenetic analyses.