An Engineered OmpG Nanopore with Displayed Peptide Motifs for Single-Molecule Multiplex Protein Detection.

Molecular detection via nanopore, achieved by monitoring changes in ionic current arising from analyte interaction with the sensor pore, is a promising technology for multiplex sensing development. Outer Membrane Protein G (OmpG), a monomeric porin possessing seven functionalizable loops, has been reported as an effective sensing platform for selective protein detection. Using flow cytometry to screen unfavorable constructs, we identified two OmpG nanopores with unique peptide motifs displayed in either loop 3 or 6, which also exhibited distinct analyte signals in single-channel current recordings. We exploited these motif-displaying loops concurrently to facilitate single-molecule multiplex protein detection in a mixture. We additionally report a strategy to increase sensor sensitivity via avidity motif display. These sensing schemes may be expanded to more sophisticated designs utilizing additional loops to increase multiplicity and sensitivity.

Infant Mortality among Adolescent Mothers in the United States: A 5-Year Analysis of Racial and Ethnic Disparities.

OBJECTIVE: This study was aimed to examine differences in infant mortality outcomes across maternal age subgroups less than 20 years in the United States with a specific focus on racial and ethnic disparities. STUDY DESIGN: Using National Center for Health Statistics cohort-linked live birth-infant death files (2009-2013) in this cross-sectional study, we calculated descriptive statistics by age (<15, 15-17, and 18-19 years) and racial/ethnic subgroups (non-Hispanic white [NHW], non-Hispanic black [NHB], and Hispanic) for infant, neonatal, and postneonatal mortality. Adjusted odds ratios (aOR) were calculated by race/ethnicity and age. Preterm birth and other maternal characteristics were included as covariates. RESULTS: Disparities were greatest for mothers <15 and NHB mothers. The risk of infant mortality among mothers <15 years compared to 18 to 19 years was higher regardless of race/ethnicity (NHW: aOR = 1.40, 95% confidence interval [CI]: 1.06-1.85; NHB: aOR = 1.28, 95% CI: 1.04-1.56; Hispanic: aOR = 1.36, 95%CI: 1.07-1.74). Compared to NHW mothers, NHB mothers had a consistently higher risk of infant mortality (15-17 years: aOR = 1.12, 95% CI: 1.03-1.21; 18-19 years: aOR = 1.21, 95% CI: 1.15-1.27), while Hispanic mothers had a consistently lower risk (15-17 years: aOR = 0.72, 95% CI: 0.66-0.78; 18-19 years: aOR = 0.74, 95% CI: 0.70-0.78). Adjusting for preterm birth had a greater influence than maternal characteristics on observed group differences in mortality. For neonatal and postneonatal mortality, patterns of disparities based on age and race/ethnicity differed from those of overall infant mortality. CONCLUSION: Although infants born to younger mothers were at increased risk of mortality, variations by race/ethnicity and timing of death existed. When adjusted for preterm birth, differences in risk across age subgroups declined and, for some racial/ethnic groups, disappeared. KEY POINTS: · Infant mortality risk was highest for adolescents <15 years old across racial/ethnic groups.. · Racial/ethnic disparities in timing of death were present even among the youngest adolescents.. · Infants of NHB adolescents had greatest risk of mortality, especially as age increased.. · Preterm birth influenced infant mortality risk, especially among NHB adolescents..

Severe Maternal Morbidity among Low-Income Patients with Hypertensive Disorders of Pregnancy.

OBJECTIVE: Hypertensive disorders of pregnancy (HDP) contribute significantly to the development of severe maternal morbidities (SMM), particularly among low-income women. The purpose of the study was to explore the relationship between maternal characteristics and SMM, and to investigate if differences in SMM exist among patients with HDP diagnosis. STUDY DESIGN: This study utilized 2017 Alabama Medicaid administrative claims. SMM diagnoses were captured using the Centers for Disease Control and Prevention's classification by International Classification of Diseases codes. Maternal characteristics and frequencies were compared using Chi-square and Cramer's V statistics. Logistic regression analyses were conducted to examine multivariable relationships between maternal characteristics and SMM among patients with HDP diagnosis. Odds ratios and 95% confidence intervals (CIs) were used to estimate risk. RESULTS: A higher proportion of patients experiencing SMM were >34 years old, Black, Medicaid for Low-Income Families eligible, lived in a county with greater Medicaid enrollment, and entered prenatal care (PNC) in the first trimester compared with those without SMM. Almost half of patients (46.2%) with SMM had a HDP diagnosis. After controlling for maternal characteristics, HDP, maternal age, county Medicaid enrollment, and trimester PNC entry were not associated with SMM risk. However, Black patients with HDP were at increased risk for SMM compared with White patients with HDP when other factors were taken into account (adjusted odds ratio [aOR] = 1.37, 95% CI: 1.11-1.69). Patients with HDP and SMM were more likely to have a prenatal hospitalization (aOR = 1.45, 95% CI: 1.20-1.76), emergency visit (aOR = 1.30, 95% CI: 1.07-1.57), and postpartum cardiovascular prescription (aOR = 2.43, 95% CI: 1.95-3.04). CONCLUSION: Rates of SMM differed by age, race, Medicaid income eligibility, and county Medicaid enrollment but were highest among patients with clinical comorbidities, especially HDP. However, among patients with HDP, Black patients had an elevated risk of severe morbidity even after controlling for other characteristics. KEY POINTS: · Patients with SMM were more likely to have a HDP diagnosis.. · Among those with HDP, Black patients had elevated risk of SMM.. · Differences in care delivery did not explain SMM disparities..

"The Ones that Care Make all the Difference": Perspectives on Student-Faculty Relationships.

Student-faculty (S-F) interactions that are conducive to students' learning can help reduce the retention and graduation gaps in higher education, especially for college students from underrepresented and underprivileged backgrounds. The aim of the study was to explore students' perceptions of their interactions with faculty, and the subjective impact of these interactions on students' academic and personal life. We analyzed qualitative data from a larger study with the goal of providing best practice models to support students experiencing displacement and food insecurity. Through purposive sampling techniques, 53 students from a diverse public university were recruited. Recruitment strategies focused on students who were likely to be facing academic, personal, and/or financial challenges that may affect their academic performance. Students were interviewed three to four times over a four to six-month period, using semi-structured interview guides. Our multidisciplinary team analyzed data thematically in team-based coding sessions using an online software. We identified four themes for faculty practices: (1) Creating Pedagogical Space, (2) Being Inclusive and Aware, (3) Being Engaged and Engaging Students, (4) Doing More Than Teaching. Based on students' perspectives, these practices lead to supportive and responsive S-F relationships that facilitate learning and success. The findings have implications related to how faculty can encourage caring S-F relationships and create conducive learning environments where students can thrive, especially during times of crisis.

Stigma, Opioids, and Public Health Messaging: The Need to Disentangle Behavior From Identity.

Stigma plays an important role in understanding successful interventions to control the opioid epidemic in the United States. Stigma has been described both as an agent to incentivize positive health behavior and as an agent of marginalization contributing to poorer health. Past scholarship has argued that stigma has positively motivated public health changes, for example, among tobacco users; it has also been associated with discrimination against vulnerable individuals, resulting in increasingly poorer health behaviors, for example in relation to HIV-prevention messaging.The discourse on stigma may conflate the denormalization of unhealthy behaviors with wholesale rejection of individual identities. More effective interventions would counter stigma against people who use opioids in general and specifically denormalize opioid misuse. These interventions might alter the effect of public health messaging and ultimately improve outcomes.We argue that public health educators and communication campaigns can contribute to positive social norm change and motivate healthy behaviors by incorporating strategies that attempt to disentangle unhealthy behaviors from identity.

Pt-, Rh-, Ru-, and Cu-Single-Wall Carbon Nanotubes Are Exceptional Candidates for Design of Anti-Viral Surfaces: A Theoretical Study.

As SARS-CoV-2 is spreading rapidly around the globe, adopting proper actions for confronting and protecting against this virus is an essential and unmet task. Reactive oxygen species (ROS) promoting molecules such as peroxides are detrimental to many viruses, including coronaviruses. In this paper, metal decorated single-wall carbon nanotubes (SWCNTs) were evaluated for hydrogen peroxide (H2O2) adsorption for potential use for designing viral inactivation surfaces. We employed first-principles methods based on the density functional theory (DFT) to investigate the capture of an individual H2O2 molecule on pristine and metal (Pt, Pd, Ni, Cu, Rh, or Ru) decorated SWCNTs. Although the single H2O2 molecule is weakly physisorbed on pristine SWCNT, a significant improvement on its adsorption energy was found by utilizing metal functionalized SWCNT as the adsorbent. It was revealed that Rh-SWCNT and Ru-SWCNT systems demonstrate outstanding performance for H2O2 adsorption. Furthermore, we discovered through calculations that Pt- and Cu-decorated SWNCT-H2O2 systems show high potential for filters for virus removal and inactivation with a very long shelf-life (2.2 × 1012 and 1.9 × 108 years, respectively). The strong adsorption of metal decorated SWCNTs and the long shelf-life of these nanomaterials suggest they are exceptional candidates for designing personal protection equipment against viruses.

Novel trimethoprim resistance gene dfrA34 identified in Salmonella Heidelberg in the USA.

Background: Trimethoprim/sulfamethoxazole is a synthetic antibiotic combination recommended for the treatment of complicated non-typhoidal Salmonella infections in humans. Resistance to trimethoprim/sulfamethoxazole is mediated by the acquisition of mobile genes, requiring both a dfr gene (trimethoprim resistance) and a sul gene (sulfamethoxazole resistance) for a clinical resistance phenotype (MIC ≥4/76 mg/L). In 2017, the CDC investigated a multistate outbreak caused by a Salmonella enterica serotype Heidelberg strain with trimethoprim/sulfamethoxazole resistance, in which sul genes but no known dfr genes were detected. Objectives: To characterize and describe the molecular mechanism of trimethoprim resistance in a Salmonella Heidelberg outbreak isolate. Methods: Illumina sequencing data for one outbreak isolate revealed a 588 bp ORF encoding a putative dfr gene. This gene was cloned into Escherichia coli and resistance to trimethoprim was measured by broth dilution and Etest. Phylogenetic analysis of previously reported dfrA genes was performed using MEGA. Long-read sequencing was conducted to determine the context of the novel dfr gene. Results and conclusions: The novel dfr gene, named dfrA34, conferred trimethoprim resistance (MIC ≥32 mg/L) when cloned into E. coli. Based on predicted amino acid sequences, dfrA34 shares less than 50% identity with other known dfrA genes. The dfrA34 gene is located in a class 1 integron in a multiresistance region of an IncC plasmid, adjacent to a sul gene, thus conferring clinical trimethoprim/sulfamethoxazole resistance. Additionally, dfrA34 is associated with ISCR1, enabling easy transmission between other plasmids and bacterial strains.

Hexadecaphyrin-(1.0.0.0.1.1.0.1.1.0.0.0.1.1.0.1): A Dual Site Ligand That Supports Thermal Conformational Changes.

A new expanded porphyrin, hexadecaphyrin-(1.0.0.0.1.1.0.1.1.0.0.0.1.1.0.1), is reported. It was obtained via the condensation of a hexapyrrolic derivative prepared in turn from a bipyrrole dialdehyde and a stable quaterpyrrole precursor. This hexadecaphyrin contains eight direct α-pyrrole-to-α-pyrrole linkages in its structure. It supports the formation of bimetallic complexes of both zinc and cobalt that are characterized by different conformational structures. Furthermore, a mixed zinc/cobalt macrocycle has been prepared. The cobalt bimetallic complex shows two stable conformations with the same oxidation state that are in equilibrium. All compounds have been characterized by common spectroscopic means, and single crystal X-ray diffraction structures were obtained for all macrocyclic compounds. DFT calculations and transient absorption spectra were used to study the electronic features of the complexes and the effect of conformational changes. This system shows promise as an accumulated heat sensor.

Proton-Coupled Redox Switching in an Annulated π-Extended Core-Modified Octaphyrin.

Proton-coupled electron transfer (PCET) is an important chemical and biological phenomenon. It is attractive as an on-off switching mechanism for redox-active synthetic systems but has not been extensively exploited for this purpose. Here we report a core-modified planar weakly antiaromatic/nonaromatic octaphyrin, namely, a [32]octaphyrin(1.0.1.0.1.0.1.0) (1) derived from rigid naphthobipyrrole and dithienothiophene (DTT) precursors, that undergoes proton-coupled two-electron reduction to produce its aromatic congener in the presence of HCl and other hydrogen halides. Evidence for the production of a [4 n + 1] π-electron intermediate radical state is seen in the presence of trifluoroacetic acid. Electrochemical analyses provide support for the notion that protonation causes a dramatic anodic shift in the reduction potentials of octaphyrin 1, thereby facilitating electron transfer from halide anions (viz. I-, Br-, and, Cl-). Electron-rich molecules, such as tetrathiafulvene (TTF), phenothiazine (PTZ), and catechol, were also found to induce PCET in the case of 1. Both the oxidized and two-electron reduced forms of 1 were characterized by X-ray diffraction analyses in the solid state and in solution via spectroscopic means.

Use of DNA aptamer for sandwich type detection of Listeria monocytogenes.

A single stranded (ss) DNA aptamer, specific to members of Listeria genus, was used to develop a two-site binding sandwich assay for capture and detection of L. monocytogenes. Antibody-immobilized immunomagnetic beads were used to capture L. monocytogenes, followed by their exposure to the aptamer detector. Detection was achieved by amplification of cell-bound aptamers by qPCR. The lower limit of detection for the combined assay was 2.5 CFU L. monocytogenes in 500 µl buffer. This is juxtaposed to a detection limit of 2.4 log10 CFU in 500 µl buffer for immunomagnetic separation coupled with qPCR detection of L. monocytogenes targeting the hly gene. When applied to turkey deli meat, subjected to 24 h of non-selective enrichment, the two-site binding sandwich assay showed positive results at initial inoculum levels of 1-2 log10 CFU per 25 g sample. Because of its lower limit of detection, the assay reported here could be useful for detection of L. monocytogenes in foods and environmental samples.

Predicting human norovirus infectivity - Recent advances and continued challenges.

Human norovirus is the leading cause of foodborne illness globally, imposing a considerable public health and economic burden. Historically, one of the major obstacles to the study of human noroviruses has been the lack of an in vitro cultivation system. In addition to hindering elucidation of viral pathogenesis, research efforts have been limited by the inability to discriminate infectious from non-infectious viral particles. Two recent breakthrough human norovirus in vitro cultivation system systems have been reported, but in their current state, may be unsuitable for routine detection or study of human noroviruses in the food and water sciences. More accessible alternative techniques utilizing molecular assays, animal models, and surrogate virus systems for prediction of human norovirus infectivity have been presented. The purpose of this review is to present the multiple recent techniques used to assess human norovirus infectivity, including recently described human norovirus in vitro cultivation systems, cultivable surrogate viruses, animal models, and alternative molecular techniques, and discuss their advantages and disadvantages in the context of determining human norovirus infectivity.

An Expanded Porphycene with High NIR Absorptivity That Stabilizes Two Different Kinds of Metal Complexes.

A new expanded porphycene with 26 π-electrons has been prepared by the McMurry coupling of 1,4-bis(3,4-diethyl-2-pyrryl)benzene dialdehyde. Expansion of the porphycene framework provides a ligand capable of stabilizing a bis(rhodium) and a monoruthenium complex. These new porphycene derivatives absorb strongly in the NIR spectral region, with appreciable absorptivity up to 1300 nm. On the basis of their ground- and excited-state spectroscopic features and structural parameters, both the free-base system and the bis(rhodium) complex are considered to be Hückel-type aromatic systems. This conclusion is supported by DFT calculations.

A plate-based histo-blood group antigen binding assay for evaluation of human norovirus receptor binding ability.

Human norovirus is a leading cause of gastroenteritis worldwide. Although two in vitro cultivation methods have been reported, they cannot provide mechanistic insights into viral inactivation. Receptor-binding assays supplement these assays and give insight into capsid integrity. We present a streamlined version of a receptor-binding assay with minimal time-to-result while maintaining accuracy and high throughput. We validate assay performance for physical and chemical inactivation treatments of a norovirus GII.4 capsid. The assay produces a high positive/negative ratio (25.3 ± 4.9) in <2.5 h and has a limit of detection of 0.1 µg/ml capsid. This method is a valuable additional tool for understanding human norovirus inactivation.

Naphthylbipyrrole-Containing Amethyrin Analogue: A New Ligand for the Uranyl (UO22+) Cation.

Using naphthobipyrrole as a functional building block, a new expanded porphyrin, naphthoisoamethyrin, was prepared in 85% yield under acid-catalyzed [4 + 2] MacDonald coupling conditions. Treatment of naphthoisoamethyrin with the nonaqueous uranyl silylamide salt [UO2[N(SiMe3)2]2·2THF] yielded the corresponding uranyl complex. Upon metalation, naphthoisoamethyrin undergoes a two-electron oxidation to yield a formal 22 π-electron aromatic species, as inferred from 1H NMR and UV-vis spectroscopy, as well as cyclic voltammetry.

Synthesis and Characterization of a Binuclear Copper(II) Naphthoisoamethyrin Complex Displaying Weak Antiferromagnetic Coupling.

The reaction between a naphthylbipyrrole-containing hexaphyrin-type expanded porphyrin and copper acetate affords a bench-stable dicopper(II) complex. UV-vis spectroscopy, cyclic voltammetry, and X-ray crystallographic analysis measurements provide support for the conclusion that this complex displays aromatic features. A weak antiferromagnetic exchange interaction between the binuclear copper(II) ions is evidenced by variable-temperature electron paramagnetic resonance and by fitting of the bulk magnetic susceptibility to a dimer model, yielding J = -5.1 cm-1.

Effectiveness of screening for craniosynostosis with ultrasound: a retrospective review.

BACKGROUND: Minimizing the ionizing radiation dose to children is fundamental to pediatric radiology. The most widely accepted imaging examination for evaluating craniosynostosis is computed tomography (CT) of the head, an examination that involves ionizing radiation. OBJECTIVE: To determine if sonography of the cranial sutures is an adequate screening examination for the diagnosis of craniosynostosis in patients with abnormal skull shape. MATERIALS AND METHODS: A retrospective review of all cranial suture ultrasound (US) examinations performed during the course of a 3-year period (July 2012 - September 2015) was undertaken. Results were compared with clinical follow-up and/or head CT to evaluate the accuracy of this modality as a screening tool to determine the presence or absence of craniosynostosis. Fifty-two sonographic exams were adequate for inclusion. RESULTS: Forty-five of the examinations did not reveal synostosis. In each of these instances, follow-up physical exam findings and/or CT imaging confirmed that no abnormal premature suture closure was present. US findings demonstrated synostosis in seven cases. CT exam or operative reports of these cases confirmed all seven findings of premature suture closure. Statistical analysis demonstrated a sensitivity of 100% (95% confidence interval [CI]: 56.1-100.0%), a specificity of 100% (95% CI: 90.2-100.0%), and a negative predictive value of 100% (95% CI: 90.2-100.0%). CONCLUSION: Cranial US is a reliable screening tool to rule out craniosynostosis in patients with abnormal head shape.

Discerning the Impact of a Lithium Salt Additive in Thin-Film Light-Emitting Electrochemical Cells with Electrochemical Impedance Spectroscopy.

Light-emitting electrochemical cells (LEECs) from small molecules, such as iridium complexes, have great potential as low-cost emissive devices. In these devices, ions rearrange during operation to facilitate carrier injection, bringing about efficient operation from simple, single-layer devices. Prior work has shown that the luminance, efficiency, and responsiveness of iridium LEECs is greatly enhanced by the inclusion of small fractions of lithium salts, but much remains to be understood about the origin of this enhancement. Recent work with planar devices demonstrates that lithium additives in iridium LEECs enhance double-layer formation. However, the quantitative influence of lithium salts on the underlying physics of conventional thin-film, sandwich structure LEECs, which beneficially operate at low voltages and generate higher luminance, has yet to be clarified. Here, we use electrochemical impedance spectroscopy to discern the impact of the lithium salt concentration on double-layer formation within the device and draw correlations with performance metrics, such as current, luminance, and external quantum efficiency.

The Influence of Simulated Organic Matter on the Inactivation of Viruses: A Review.

Viruses impose a significant public health burden globally, and one of the key elements in controlling their transmission is the ability to inactivate them using disinfectants. However, numerous challenges to inactivating foodborne viruses exist due to inherent viral characteristics (such as recalcitrance to commonly used inactivation agents) and external factors (such as improper cleaning before application of inactivation agent, improper contact time, etc.). Given the potential for improper application of disinfectants (such as shorter than recommended contact time, improper disinfectant concentration, etc.), understanding the performance of a disinfectant in the presence of an organic load is important. To accomplish this, the introduction of simulated organic loads is often used when studying the efficacy of a disinfectant against different viruses. However, the different types of simulated organic loads used in foodborne virus inactivation studies or their relative effects on inactivation have not been reviewed. The purpose of this review is to survey different simulated organic load formulations used in studying foodborne virus inactivation, as well as present and compare the influence of these different formulations on viral inactivation. The findings included in this review suggest that many simulated organic load formulations can reduce disinfectants' efficacy against viruses. Based on the findings in this review, blood, particularly serum or feces, are among the most commonly used and efficacious forms of simulated organic load in many tests.

Sample Processing and Concentration Methods for Viruses from Foods and the Environment Prior to Detection.

Viruses are the leading cause of foodborne illness globally. Concentration of viruses from samples is important for detection because viral contamination of foods often occurs at low levels. In general, virus concentration methods can be classified as either nonspecific, exploiting the relatively homogeneous physicochemical properties of the virus to separate/concentrate it from the sample matrix, or specific, relying on recognition elements such as antibodies to specifically capture and separate viruses from foods. Numerous nonspecific and specific techniques for virus concentration have been reported, each with its own advantages and limitations. Factors to consider can include reagent and equipment costs, time-to-result, ease of use, and potential to eliminate matrix-associated inhibitors. The purpose of this review is to survey the different foodborne virus concentration techniques and their efficacy in various food and environmental matrices as well as discuss some emerging techniques for purification and concentration of viral pathogens from food samples.