Formulation, inflammation, and RNA sensing impact the immunogenicity of self-amplifying RNA vaccines

To be effective, RNA vaccines require both in situ translation and the induction of an immune response to recruit cells to the site of immunization. These factors can pull in opposite directions with the inflammation reducing expression of the vaccine antigen. We investigated how formulation affects the acute systemic cytokine response to a self-amplifying RNA (saRNA) vaccine. We compared a cationic polymer (pABOL), a lipid emulsion (nanostructured lipid carrier, NLC), and three lipid nanoparticles (LNP). After immunization, we measured serum cytokines and compared the response to induced antibodies against influenza virus. Formulations that induced a greater cytokine response induced a greater antibody response, with a significant correlation between IP-10, MCP-1, KC, and antigen-specific antibody titers. We then investigated how innate immune sensing and signaling impacted the adaptive immune response to vaccination with LNP-formulated saRNA. Mice that lacked MAVS and are unable to signal through RIG-I-like receptors had an altered cytokine response to saRNA vaccination and had significantly greater antibody responses than wild-type mice. This indicates that the inflammation induced by formulated saRNA vaccines is not solely deleterious in the induction of antibody responses and that targeting specific aspects of RNA vaccine sensing might improve the quality of the response

Inductively guided circuits for ultracold dressed atoms

Recent progress in optics, atomic physics and material science has paved the way to study quantum effects in ultracold atomic alkali gases confined to non-trivial geometries. Multiply connected traps for cold atoms can be prepared by combining inhomogeneous distributions of DC and radio-frequency electromagnetic fields with optical fields that require complex systems for frequency control and stabilization. Here we propose a flexible and robust scheme that creates closed quasi-one-dimensional guides for ultracold atoms through the ‘dressing’ of hyperfine sublevels of the atomic ground state, where the dressing field is spatially modulated by inductive effects over a micro-engineered conducting loop. Remarkably, for commonly used atomic species (for example, 7Li and 87Rb), the guide operation relies entirely on controlling static and low-frequency fields in the regimes of radio-frequency and microwave frequencies. This novel trapping scheme can be implemented with current technology for micro-fabrication and electronic control

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The accuracy of MRI in the detection of Lumbar Disc Containment

<p>Abstract</p> <p>Background</p> <p>MRI has proven to be an extremely valuable tool in the assessment of normal and pathological spinal anatomy. Accordingly, it is commonly used to assess containment of discal material by the outer fibers of the anulus fibrosus and posterior longitudinal ligaments. Determination of such containment is important to determine candidacy for intradiscal techniques and has prognostic significance. The accuracy of MRI in detecting containment has been insufficiently documented.</p> <p>Methods</p> <p>The MRI's of fifty consecutive patients undergoing open lumbar microdiscectomy were prospectively evaluated for disc containment by a neuroradiologist and senior spinal surgeon using criteria available in the literature and the classification of Macnab/McCulloch. An independent surgeon then performed the surgery and documented the actual containment status using the same methods. Statistical evaluation of accuracy was undertaken.</p> <p>Results</p> <p>MRI was found to be 72% sensitive, 68% specific, and 70% accurate in detecting containment status of lumbar herniated discs.</p> <p>Conclusion</p> <p>MRI may be inaccurate in assessing containment status of lumbar disc herniations in 30% of cases. Given the importance of containment for patient selection for indirect discectomy techniques and intradiscal therapies, coupled with prognostic significance; other methods to assess containment should be employed to assess containment when such alternative interventions are being considered.</p

English language proficiency and the accommodations for language non-concordance amongst patients utilizing chiropractic college teaching clinics

Background: The number of households in the United States that are not proficient in the English language is growing and presenting a challenge to the health care system. Over nineteen percent of the US population speak a language other than English in the home. This increase in language discordance generates a greater need to find and implement accommodations in the clinical setting to insure accurate and efficient diagnosis and treatment as well as provide for patient safety. Aim: The purpose of this study is to determine the percentage of patients accessing the chiropractic college teaching clinics who are not proficient in the English language and to what extent the colleges provide accommodations for that language disparity. Methods: The clinic directors and deans of the Association of Chiropractic Colleges were surveyed via an on-line survey engine. The survey queried the percentage of the patient population that is not English language proficient, the accommodations the college currently has in place, if the college has a language specific consent to treat document and if the college has a written policy concerning patients without English proficiency. Results: Fifty percent of the contacted chiropractic colleges responded to the survey. In the respondent college clinics 16.5% of the patient population is not proficient in English, with over 75% speaking Spanish. All but one of the respondents provide some level of accommodation for the language non-concordance. Forty five percent of the responding colleges employ a language specific consent to treat form. The implementation of accommodations and the use of a language specific consent to treat form is more prevalent at colleges with a higher percentage of non-English speaking patients. Conclusions: The percentage of patients with limited English proficiency accessing services at the teaching clinics of the chiropractic colleges mirrors the numbers in the general population. There is a wide disparity in the accommodations that the individual colleges make to address this language discordance. There is a need to further develop accurate and meaningful accommodations to address language disparity in the chiropractic teaching clinics.https://doi.org/10.1186/2045-709X-21-

Real-time PCR-based assay to quantify the relative amount of human and mouse tissue present in tumor xenografts

<p>Abstract</p> <p>Background</p> <p>Xenograft samples used to test anti-cancer drug efficacies and toxicities in vivo contain an unknown mix of mouse and human cells. Evaluation of drug activity can be confounded by samples containing large amounts of contaminating mouse tissue. We have developed a real-time quantitative polymerase chain reaction (qPCR) assay using TaqMan technology to quantify the amount of mouse tissue that is incorporated into human xenograft samples.</p> <p>Results</p> <p>The forward and reverse primers bind to the same DNA sequence in the human and the mouse genome. Using a set of specially designed fluorescent probes provides species specificity. The linearity and sensitivity of the assay is evaluated using serial dilutions of single species and heterogeneous DNA mixtures. We examined many xenograft samples at various in vivo passages, finding a wide variety of human:mouse DNA ratios. This variation may be influenced by tumor type, number of serial passages in vivo, and even which part of the tumor was collected and used in the assay.</p> <p>Conclusions</p> <p>This novel assay provides an accurate quantitative assessment of human and mouse content in xenograft tumors. This assay can be performed on aberrantly behaving human xenografts, samples used in bioinformatics studies, and periodically for tumor tissue frequently grown by serial passage in vivo.</p

Clinical decision-making to facilitate appropriate patient management in chiropractic practice: 'the 3-questions model'

Background A definitive diagnosis in chiropractic clinical practice is frequently elusive, yet decisions around management are still necessary. Often, a clinical impression is made after the exclusion of serious illness or injury, and care provided within the context of diagnostic uncertainty. Rather than focussing on labelling the condition, the clinician may choose to develop a defendable management plan since the response to treatment often clarifies the diagnosis. Discussion This paper explores the concept and elements of defensive problem-solving practice, with a view to developing a model of agile, pragmatic decision-making amenable to real-world application. A theoretical framework that reflects the elements of this approach will be offered in order to validate the potential of a so called '3-Questions Model'; Summary Clinical decision-making is considered to be a key characteristic of any modern healthcare practitioner. It is, thus, prudent for chiropractors to re-visit the concept of defensible practice with a view to facilitate capable clinical decision-making and competent patient examination skills. In turn, the perception of competence and trustworthiness of chiropractors within the wider healthcare community helps integration of chiropractic services into broader healthcare settings

Effect of pathology type and severity on the distribution of MRI signal intensities within the degenerated nucleus pulposus: application to idiopathic scoliosis and spondylolisthesis

<p>Abstract</p> <p>Background</p> <p>Disc degeneration is characterized by a loss of cellularity, degradation of the extracellular matrix, and, as a result, morphological changes and biomechanical alterations. We hypothesized that the distribution of the MR signal intensity within the nucleus zone of the intervertebral disc was modified according to the pathology and the severity of the pathology. The objective of this study was to propose new parameters characterizing the distribution of the signal intensity within the nucleus zone of lumbar intervertebral discs, and to quantify these changes in patients suffering from spondylolisthesis or idiopathic scoliosis.</p> <p>Methods</p> <p>A retrospective study had been performed on T2-weighted MR images of twenty nine patients suffering from spondylolisthesis and/or scoliosis. The high intensity zone of the nucleus pulposus was semi-automatically detected. The distance "DX" between the center weighted by the signal intensity and the geometrical center was quantified. The sum of the signal intensity on the axis perpendicular to the longitudinal axis of the disc was plotted for each position of the longitudinal axis allowing defining the maximum sum "SM" and its position "PSM".</p> <p>Results</p> <p>"SM" was clearly higher and "PSM" was more shifted for scoliosis than for spondylolisthesis. A two-way analysis of variance showed that the differences observed on "DX" were not attributed to the pathology nor its severity, the differences observed on "SM" were attributed to the pathology but not to its severity, and the differences observed on "PSM" were attributed to both the pathology and its severity.</p> <p>Conclusions</p> <p>The technique proposed in this study showed significant differences in the distribution of the MR signal intensity within the nucleus zone of intervertebral discs due to the pathology and its severity. The dependence of the "PSM" parameter to the severity of the pathology suggests this parameter as a predictive factor of the pathology progression. This new technique should be useful for the early diagnosis of intervertebral disc pathologies as it highlights abnormal patterns in the MRI signal for low severity of the pathology.</p

Results from the translation and adaptation of the Iranian Short-Form McGill Pain Questionnaire (I-SF-MPQ): preliminary evidence of its reliability, construct validity and sensitivity in an Iranian pain population

<p>Abstract</p> <p>Background</p> <p>The Short Form McGill Pain Questionnaire (SF-MPQ) is one of the most widely used instruments to assess pain. The aim of this study was to translate and culturally adapt the questionnaire for Farsi (the official language of Iran) speakers in order to test its reliability and sensitivity.</p> <p>Methods</p> <p>We followed Guillemin's guidelines for cross-cultural adaption of health-related measures, which include forward-backward translations, expert committee meetings, and face validity testing in a pilot group. Subsequently, the questionnaire was administered to a sample of 100 diverse chronic pain patients attending a tertiary pain and rehabilitation clinic. In order to evaluate test-retest reliability, patients completed the questionnaire in the morning and early evening of their first visit. Finally, patients were asked to complete the questionnaire for the third time after completing a standardized treatment protocol three weeks later. Intraclass correlation coefficient (ICC) was used to evaluate reliability. We used principle component analysis to assess construct validity.</p> <p>Results</p> <p>Ninety-two subjects completed the questionnaire both in the morning and in the evening of the first visit (test-retest reliability), and after three weeks (sensitivity to change). Eight patients who did not finish treatment protocol were excluded from the study. Internal consistency was found by Cronbach's alpha to be 0.951, 0.832 and 0.840 for sensory, affective and total scores respectively. ICC resulted in 0.906 for sensory, 0.712 for affective and 0.912 for total pain score. Item to subscale score correlations supported the convergent validity of each item to its hypothesized subscale. Correlations were observed to range from r²= 0.202 to r²= 0.739. Sensitivity or responsiveness was evaluated by pair t-test, which exhibited a significant difference between pre- and post-treatment scores (p < 0.001).</p> <p>Conclusion</p> <p>The results of this study indicate that the Iranian version of the SF-MPQ is a reliable questionnaire and responsive to changes in the subscale and total pain scores in Persian chronic pain patients over time.</p