The Potential of Probiotics as Ingestible Adjuvants and Immune Modulators for Antiviral Immunity and Management of SARS-CoV-2 Infection and COVID-19.

Probiotic bacteria are able to modulate general antiviral responsiveness, including barrier functionality and innate and adaptive immune responses. The COVID-19 pandemic, resulting from SARS-CoV-2 infection, has created a need to control and treat this viral infection and its ensuing immunopathology with a variety of approaches; one such approach may involve the administration of probiotic bacteria. As with most viral infections, its pathological responses are not fully driven by the virus, but are significantly contributed to by the host's immune response to viral infection. The potential adoption of probiotics in the treatment of COVID-19 will have to appreciate the fine line between inducing antiviral immunity without over-provoking immune inflammatory responses resulting in host-derived immunopathological tissue damage. Additionally, the effect exerted on the immune system by SARS-CoV-2 evasion strategies will also have to be considered when developing a robust response to this virus. This review will introduce the immunopathology of COVID-19 and the immunomodulatory effects of probiotic strains, and through their effects on a range of respiratory pathogens (IAV, SARS-CoV, RSV), as well as SARS-CoV-2, will culminate in a focus on how these bacteria can potentially manipulate both infectivity and immune responsiveness via barrier functionality and both innate and adaptive immunity. In conclusion, the harnessing of induction and augmentation of antiviral immunity via probiotics may not only act as an ingestible adjuvant, boosting immune responsiveness to SARS-CoV-2 infection at the level of barrier integrity and innate and adaptive immunity, but also act prophylactically to prevent infection and enhance protection afforded by current vaccine regimens.

Addressing serious and continuing research noncompliance and integrity violations through action plans: Interviews with institutional officials.

Serious and continuing research noncompliance and integrity violations undermine the quality of research and trust in science. When researchers engage in these behaviors, institutional officials (IOs) often develop corrective action plans. Ideally, such plans address the root causes so noncompliance or research integrity violations discontinue. The aim of this study was to identify what IOs perceive as causes and action plan activities typically prescribed. We conducted semi-structured in-depth interviews with 47 IOs at research institutions across the U.S. including: institutional review board and institutional animal care and use committee chairs and directors, chief research officers, research compliance and integrity officers, and institutional conflicts of interest chairs and directors. The most common root causes identified were: 1) lack of knowledge or training, 2) failure to provide research team supervision, and 3) researcher attitudes toward compliance. The most common action plan activities include: 1) retraining in compliance or research integrity, 2) follow-up and hands-on involvement with the researcher, and 3) mandated oversight or mentoring. Because the most commonly identified action plan activities fail to adequately address the majority of root causes, our findings suggest a need for IOs to rethink existing approaches to action plan development to more effectively target root causes.

Kinetic intermediates of holo- and apo-myoglobin studied using HDX-TIMS-MS and molecular dynamic simulations.

In the present work, the kinetic intermediates of holo- and apo-myoglobin were studied by correlating the ion-neutral collision cross section and time resolved H/D back exchange rate simultaneously in a trapped ion mobility spectrometer coupled to a mass spectrometer (HDX-TIMS-MS). The high mobility resolution of the TIMS cell permitted the observation of multiple IMS bands and complementary molecular dynamics simulations resulted in the assignment of candidate structures for each experimental condition studied (e.g., holo [M + 8H](+8)-[M + 9H](+9) and apo [M + 9H](+9)-[M + 19H](+19)). Inspection of the kinetic intermediates suggests that the tertiary structure of apomyoglobin unfolds quickly upon the loss of the Fe protoporphyrin IX that stabilizes the interactions between the A, G, and H helices. In the absence of the porphyrin heme, the apomyoglobin unfolds to Xn kinetic intermediates that vary in the extent of unfolding as a result of the observed charge state.

Changes in lipid distribution in E. coli strains in response to norfloxacin.

Bacterial resistance to antibiotics has become an increasing threat, requiring not only the development of new targets in drug discovery, but more importantly, a better understanding of cellular response. In the current study, three closely related Escherichia coli strains, a wild type (MG1655) and an isogenic pair derived from the wild type (DPB635 and DPB636) are studied following exposure to sub lethal concentrations of antibiotic (norfloxacin) over time. In particular, genotype similarities between the three strains were assessed based on the lipid regulation response (e.g. presence/absence and up/down regulation). Lipid identification was performed using direct surface probe analysis (matrix-assisted laser desorption/ionization, MALDI), coupled to high-resolution mass spectrometry (Fourier transform ion cyclotron resonance mass spectrometry, FT-ICR MS) followed by statistical analysis of variability and reproducibility across batches using internal standards. Inspection of the lipid profile showed that for the MG1655, DPB635 and DPB636 E. coli strains, a similar distribution of the altered lipids was observed after exposure to norfloxacin antibiotic (e.g. fatty acids and glycerol phospholipids are up and down regulated, respectively). Additionally, variations in the lipid distribution resemble the extent to which each strain can combat the antibiotic exposure. That is, the topA66 topoisomerase I mutation of DPB636 translates into diminished response related to antibiotic sensitivity when compared to MG1655 and the DPB635 strains.

Measuring kidney patients' motivation to pursue living donor kidney transplant: development of stage of change, decisional balance and self-efficacy measures.

While educational interventions to increase patient motivation to pursue living donor kidney transplant have shown success in increasing living donor kidney transplant rates, there are no validated, theoretically consistent measures of Stage of Change, a measure of readiness to pursue living donor kidney transplant; Decisional Balance, a weighted assessment of living donor kidney transplant's advantages/disadvantages; and Self-Efficacy, a measure of belief that patients can pursue living donor kidney transplant in difficult circumstances. This study developed and validated measures of these three constructs. In two independent samples of kidney patients (N 1 = 279 and N 2 = 204), results showed good psychometric properties and support for their use in the assessment of living donor kidney transplant interventions.

Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space.

The ability to correlate experimental ion mobility data with candidate structures from theoretical modeling provides a powerful analytical and structural tool for the characterization of biomolecules. In the present paper, a theoretical workflow is described to generate and assign candidate structures for experimental trapped ion mobility and H/D exchange (HDX-TIMS-MS) data following molecular dynamics simulations and statistical filtering. The applicability of the theoretical predictor is illustrated for a peptide and protein example with multiple conformations and kinetic intermediates. The described methodology yields a low computational cost and a simple workflow by incorporating statistical filtering and molecular dynamics simulations. The workflow can be adapted to different IMS scenarios and CCS calculators for a more accurate description of the IMS experimental conditions. For the case of the HDX-TIMS-MS experiments, molecular dynamics in the "TIMS box" accounts for a better sampling of the molecular intermediates and local energy minima.

Your Path to Transplant: a randomized controlled trial of a tailored computer education intervention to increase living donor kidney transplant.

BACKGROUND: Because of the deceased donor organ shortage, more kidney patients are considering whether to receive kidneys from family and friends, a process called living donor kidney transplantation (LDKT). Although Blacks and Hispanics are 3.4 and 1.5 times more likely, respectively, to develop end stage renal disease (ESRD) than Whites, they are less likely to receive LDKTs. To address this disparity, a new randomized controlled trial (RCT) will assess whether Black, Hispanic, and White transplant patients' knowledge, readiness to pursue LDKT, and receipt of LDKTs can be increased when they participate in the Your Path to Transplant (YPT) computer-tailored intervention. METHODS/DESIGN: Nine hundred Black, Hispanic, and White ESRD patients presenting for transplant evaluation at University of California, Los Angeles Kidney and Pancreas Transplant Program (UCLA-KPTP) will be randomly assigned to one of two education conditions, YPT or Usual Care Control Education (UC). As they undergo transplant evaluation, patients in the YPT condition will receive individually-tailored telephonic coaching sessions, feedback reports, video and print transplant education resources, and assistance with reducing any known socioeconomic barriers to LDKT. Patients receiving UC will only receive transplant education provided by UCLA-KPTP. Changes in transplant knowledge, readiness, pros and cons, and self-efficacy to pursue LDKT will be assessed prior to presenting at the transplant center (baseline), during transplant evaluation, and 4- and 8-months post-baseline, while completion of transplant evaluation and receipt of LDKTs will be assessed at 18-months post-baseline. The RCT will determine, compared to UC, whether Black, Hispanic, and White patients receiving YPT increase in their readiness to pursue LDKT and transplant knowledge, and become more likely to complete transplant medical evaluation and pursue LDKT. It will also examine how known patient, family, and healthcare system barriers to LDKT act alone and in combination with YPT to affect patients' transplant decision-making and behavior. Statistical analyses will be performed under an intent-to-treat approach. DISCUSSION: At the conclusion of the study, we will have assessed the effectiveness of an innovative and cost-effective YPT intervention that could be utilized to tailor LDKT discussion and education based on the needs of individual patients of different races in many healthcare settings. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02181114.

Lung transplant or bust: patients' recommendations for ideal lung transplant education.

CONTEXT: Effective lung transplant education helps ensure informed decision making by patients and better transplant outcomes. OBJECTIVE: To understand the educational needs and experiences of lung transplant patients. DESIGN: Mixed-method study employing focus groups and patient surveys. SETTING: Barnes-Jewish Hospital in St Louis, Missouri. PATIENTS: 50 adult lung transplant patients: 23 pretransplant and 27 posttransplant. MAIN OUTCOME MEASURES: Patients' interest in receiving specific transplant information, the stage in the transplant process during which they wanted to receive the education, and the preferred format for presenting the information. RESULTS: Patients most wanted information about how to sustain their transplant (72%), when to contact their coordinator immediately (56%), transplant benefits (56%), immunosuppressants (54%), and possible out-of-pocket expenses (52%). Patients also wanted comprehensive information early in the transplant process and a review of a subset of topics immediately before transplant (time between getting the call that a potential donor has been found and getting the transplant). Patients reported that they would use Internet resources (74%) and converse with transplant professionals (68%) and recipients (62%) most often. DISCUSSION: Lung transplant patients are focused on learning how to get a transplant and ensuring its success afterwards. A comprehensive overview of the evaluation, surgery, and recovery process at evaluation onset with a review of content about medications, pain management, and transplant recovery repeated immediately before surgery is ideal.

Discrimination of unprocessed cotton on the basis of geographic origin using multi-element stable isotope signatures.

RATIONALE: Cotton is the most commonly used natural plant product for the manufacture of yarns and textiles. Consumer perception regarding differences in textile quality in relation to geographic provenance of cotton as well as stringent product labelling requirements demand for the supply chain to furnish proof of geographic provenance beyond merely paper-based audit trails. METHODS: We have applied isotope ratio mass spectrometry to generate multivariate data sets of raw cotton. A two-point equilibration process with water at ambient temperature was used to account for hydrogen exchange between free hydroxyl groups in the cellulose lattice at ambient humidity, prior to hydrogen isotope analysis. RESULTS: The molar fraction of exchangeable hydrogen in cotton at ambient temperature was found to be 0.046, which is in good agreement with the expected exchange fraction of 0.05. Hierarchical cluster analysis of multivariate stable isotope abundance data from 17 US cotton and 15 non-US cotton samples was able to cluster 15 of the 17 US cotton samples in one group. CONCLUSIONS: Hierarchical cluster analysis of multivariate stable isotope signatures of raw cotton showed great promise as an analytical tool to differentiate between US and non-US cotton and possibly even to be able to group unprocessed cotton according to geographic origin.

Direct observation of differences of carotenoid polyene chain cis/trans isomers resulting from structural topology.

In the present paper, trapped ion mobility spectrometry (TIMS) and theoretical calculations have been used to study carotenoid geometrical motifs generated by photoisomerization from the all-trans geometry. Multiple geometric isomers of the carotenoids lutein and zeaxanthin were separated using TIMS (R > 110) for [M](+), [M + H](+), and [M - 18](+) molecular species. Comparison of observed cross sections with those obtained from molecular dynamics calculations showed that the number of cis double bonds and s-cis single bonds in the polyene chain determine the topology space of the carotenoid. The intensities of IMS signals are correlated with the relative stability of these geometric isomers.1,2 The most stable isomer is the all-trans geometry regardless of the ionization state ([M - 18](+), [M](+), and [M + H](+)), and structural stability decreases with the increasing number of cis and/or s-cis bonds in the polyene chain.

Isomerization kinetics of AT hook decapeptide solution structures.

The mammalian high mobility group protein HMGA2 contains three DNA binding motifs associated with many physiological functions including oncogenesis, obesity, stem cell youth, human height, and human intelligence. In the present paper, trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) has been utilized to study the conformational dynamics of the third DNA binding motif using the "AT hook" decapeptide unit (Lys(1)-Arg(2)-Prol(3)-Arg(4)-Gly(5)-Arg(6)-Prol(7)-Arg(8)-Lys(9)-Trp(10), ATHP) as a function of the solvent state. Solvent state distributions were preserved during electrospray ion formation, and multiple IMS bands were identified for the [M + 2H](2+) and for the [M + 3H](3+) charge states. Conformational isomer interconversion rates were measured as a function of the trapping time for the [M + 2H](2+) and [M + 3H](3+) charge states. Candidate structures were proposed for all IMS bands observed. Protonation site, proline residue conformation, and side chain orientations were identified as the main motifs governing the conformational interconversion processes. Conformational dynamics from the solvent state distribution to the gas-phase "de-solvated" state distribution demonstrated that ATHP is "structured", and relative abundances are associated with the relative stability between the proposed conformers. The most stable ATHP [M + 2H](2+) conformation at the "de-solvated" state corresponds to the AT hook motif observed in AT-rich DNA regions.

Modifiable patient characteristics and racial disparities in evaluation completion and living donor transplant.

BACKGROUND AND OBJECTIVES: To reduce racial disparities in transplant, modifiable patient characteristics associated with completion of transplant evaluation and receipt of living donor kidney transplant must be identified. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 2004 to 2007, 695 black and white patients were surveyed about 15 less-modifiable and 10 more-modifiable characteristics at evaluation onset; whether they had completed evaluation within 1 year and received living donor kidney transplants by 2010 was determined. Logistic regression and competing risks time-to-event analysis were conducted to determine the variables that predicted evaluation completion and living donor kidney transplant receipt. RESULTS: Not adjusting for covariates, blacks were less likely than whites to complete evaluation (26.2% versus 51.8%, P<0.001) and receive living donor kidney transplants (8.7% versus 21.9%, P<0.001). More-modifiable variables associated with completing evaluation included more willing to be on the waiting list (odds ratio=3.4, 95% confidence interval=2.1, 5.7), more willing to pursue living donor kidney transplant (odds ratio=2.7, 95% confidence interval=1.8, 4.0), having access to more transplant education resources (odds ratio=2.2, 95% confidence interval=1.5, 3.2), and having greater transplant knowledge (odds ratio=1.8, 95% confidence interval=1.2, 2.7). Patients who started evaluation more willing to pursue living donor kidney transplant (hazard ratio=4.3, 95% confidence interval=2.7, 6.8) and having greater transplant knowledge (hazard ratio=1.2, 95% confidence interval=1.1, 1.3) were more likely to receive living donor kidney transplants. CONCLUSIONS: Because patients who began transplant evaluation with greater transplant knowledge and motivation were ultimately more successful at receiving transplants years later, behavioral and educational interventions may be very successful strategies to reduce or overcome racial disparities in transplant.

Elemental analysis of glass by laser ablation inductively coupled plasma optical emission spectrometry (LA-ICP-OES).

The elemental analysis of glass evidence has been established as a powerful discrimination tool for forensic analysts. Laser ablation inductively coupled plasma optical emission spectrometry (LA-ICP-OES) has been compared to laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and energy dispersive micro X-ray fluorescence spectroscopy (µXRF/EDS) as competing instrumentation for the elemental analysis of glass. The development of a method for the forensic analysis of glass coupling laser ablation to ICP-OES is presented for the first time. LA-ICP-OES has demonstrated comparable analytical performance to LA-ICP-MS based on the use of the element menu, Al (Al I 396.15 nm), Ba (Ba II 455.40 nm), Ca (Ca II 315.88 nm), Fe (Fe II 238.20 nm), Li (Li I 670.78 nm), Mg (Mg I 285.21 nm), Sr (Sr II 407.77 nm), Ti (Ti II 368.51 nm), and Zr (Zr II 343.82 nm). The relevant figures of merit, such as precision, accuracy and sensitivity, are presented and compared to LA-ICP-MS. A set of 41 glass samples was used to assess the discrimination power of the LA-ICP-OES method in comparison to other elemental analysis techniques. This sample set consisted of several vehicle glass samples that originated from the same source (inside and outside windshield panes) and several glass samples that originated from different vehicles. Different match criteria were used and compared to determine the potential for Type I and Type II errors. It was determined that broader match criteria is more applicable to the forensic comparison of glass analysis because it can reduce the affect that micro-heterogeneity inherent in the glass fragments and a less than ideal sampling strategy can have on the interpretation of the results. Based on the test set reported here, a plus or minus four standard deviation (± 4s) match criterion yielded the lowest possibility of Type I and Type II errors. The developed LA-ICP-OES method has been shown to perform similarly to LA-ICP-MS in the discrimination among different sources of glass while offering the advantages of a lower cost of acquisition and operation of analytical instrumentation making ICP-OES a possible alternative elemental analysis method for the forensic laboratory.

Characterizing the infrared bands of aqueous soluble silicates.

A systematic study of the transition in silicate solutions from a solution containing a highly complex mixture of silicate species to one dominated by a single symmetric cubic octamer has been completed. Infrared and NMR results have been analyzed and compared with each other and literature values. The FT-IR band locations are dependent on many factors, particularly the dominant band near 1000 cm(-1). The analysis supports Dent Glasser's hypothesis that silica polymerization results from changes in distribution between the larger colloidal silica and intermediate sized anionic fraction rather than the continuous stepwise growth seen with organic polymerization. A constant value of silica monomer seen in all solutions independent of the complexity of the species or their distribution suggests equilibrium between the monomeric form and larger anions and polymers that is independent of their structure. No evidence is uncovered for specific silicate species dependent IR band assignments.