Granthamchristensen5681

We also provide detailed protocols for dissecting and isolating DRG (the site of HSV-2 latency), quantifying HSV-2 genomic copies in DRG, and assessing symptomatic and subclinical shedding of HSV-2 in the vagina. © 2021 Wiley Periodicals LLC. Basic Protocol 1 Primary and recurrent genital herpes infection in the guinea pig model Support Protocol 1 Blood collection via lateral saphenous vein or by cardiac puncture after euthanasia Support Protocol 2 Dissection and isolation of dorsal root ganglia from guinea pigs Support Protocol 3 PCR amplification and quantification of HSV-2 genomic DNA from samples Basic Protocol 2 Primary genital herpes infection in the mouse model Alternate Protocol Flank infection with HSV-2 in the mouse model Support Protocol 4 Dissection and isolation of mouse dorsal root ganglia.To avoid excluding individuals with limited English proficiency from participating in research, the consent form and other documents should be presented to them in their primary language and in a format that is understandable. However, evidence suggests that, when documents are translated for prospective and actual research participants with limited English proficiency, these individuals often fail to engage with the documents and the research in the same terms as their English-speaking counterparts do. We argue that this is because methodological challenges remain after a decision to translate has been made. This study investigated how translation approaches affected reader response and intelligibility. Participants were asked to review two translated versions of a survey (which reflected a functionalist and a literal approach to translation) followed by semistructured interviews. Quantitative and qualitative analysis revealed a preference for a functionalist translation and a higher number of problems raised in regard to the literal translation. The recommendations we offer here include considering the most appropriate translation approach for a specific genre and purpose.Biobank participants often do not understand the information they are provided during the informed consent process. Ethicists and other stakeholders have disagreed, however, on the appropriate response to these failures in understanding. This paper describes an attempt to address this issue by conducting knowledge tests with 22 recent biobank enrollees, followed by in-depth, semistructured interviews about the goal of understanding in biobank consent. The interviews revealed that while biobank enrollees thought the information on the knowledge test was important, they did not think that performance on the test should affect whether individuals are permitted to enroll in a biobank. Three main themes emerged from the interviews helping others by contributing to research is more important than understanding consent forms, less understanding is required because biobank-based research is low risk, and only a small amount of information in the consent form is really essential. These perspectives should be considered in discussing the ethics and governance of biobank consent processes.In this article, we analyze legal and ethical issues raised in Big Data health research projects in the Covid-19 era and consider how these issues might be addressed in ways that advance positive values (e.g., furtherance of respect for persons and accordance with relevant legal frameworks) while mitigating or eliminating any negative aspects (e.g., exacerbation of social inequality and injustice). We apply this analysis specifically to UK-REACH (The United Kingdom Research Study into Ethnicity and Covid-19 Outcomes in Healthcare Workers), a project with which we are involved. We argue that Big Data projects like UK-REACH can be conducted in an ethically robust manner and that funders and sponsors ought to encourage similar projects to drive better evidence-based public policy in public health. As part of this, we advocate that a Big Data ethics-by-design approach be undertaken when such projects are constructed. This principle extends the work of those who advocate ethics by design by addressing prominent issues in Big Data health research projects; it holds that ethical values and principles in Big Data health research projects are best adhered to when they are already integrated into the project aims and methods at the design stage. In advocating this principle, we present a unique perspective regarding pressing ethical problems around large-scale, data-driven Covid-19 research, as well as legal issues associated with processing ostensibly anonymized health data.

Nociplastic concept incorporates a broad continuum of pain phenotypes shared with clinical peculiarity. This study aimed to develop and validate a diagnostic tool, the preliminary Nociplastic-based Fibromyalgia Features (NFF), to detect fibromyalgia (FM) in patients with chronic pain.

Items requiring yes or no responses and relating to the most relevant clinical nociplastic pain (NP) features of FM were compiled by a group of expert rheumatologists. The provisional list was tested in a prospective study on 185 consecutive patients with chronic pain (126 patients with FM and 59 patients with non-FM non-inflammatory chronic pain) diagnosed based on expert decision. Identification of the most discriminant combinations of items for FM and the calculation of their sensitivity and specificity were based on both univariate and multivariate (stepwise logistic regression) analyses. All participants were investigated through the final NFF, the 2011 American College of Rheumatology (ACR) criteria, and the 2016 ACR criteria. NFF performance was assessed with receiver operating characteristic curve analysis.

Based on multivariate analyses, we retained only seven items in the final version of the NFF. A cut-off score of 4 (corresponding to the number of positive items) gave the highest rate of correct identification of patients (85%), with a sensitivity of 82% and a specificity of 91%. The NFF showed the highest concordance rate with expert diagnosis (85%) and the lowest value (77%) with the ACR 2016 criteria.

The preliminary NFF with respect to the various aspects of NP showed good performance for detection of the FM in the clinical setting. This tool may provide a more pragmatic approach to the timely diagnosis of FM.

The preliminary NFF with respect to the various aspects of NP showed good performance for detection of the FM in the clinical setting. This tool may provide a more pragmatic approach to the timely diagnosis of FM.

Endoscopic sinus surgery (ESS) and septoplasty are commonly performed procedures without standardized postoperative pain regimens. There is reluctance to prescribe opioids for postoperative pain given their potential for abuse. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to reduce or even obviate the need for opioid pain medications after otolaryngologic surgeries, but prospective validation is lacking.

A randomized, controlled study comparing the efficacy of diclofenac sodium to hydrocodone/acetaminophen (APAP) after ESS with or without septoplasty was performed. Participants were given a 100-mm visual analog pain scale (VAS) at postoperative days (PODs) 1, 2, 3, and 5 after ESS. Two-sample t tests were used to compare pain scores between groups.

One hundred patients enrolled, and 74 patients provided pain scores to the survey. Pain was greatest for both groups on POD 1. Treatment with diclofenac sodium vs hydrocodone/APAP did not statistically impact pain scores at PODs 1, 2, 3, or 5. No cases of epistaxis requiring an emergency room visit or return to the operating room were noted during the study period.

Diclofenac sodium may be non-inferior to hydrocodone/APAP in treating pain after ESS with or without septoplasty in opioid naive patients without pre-existing pain conditions. Navitoclax in vivo Further studies with larger samples are warranted to investigate the potential superiority of diclofenac to hydrocodone/APAP in certain patients after ESS and septoplasty.

Diclofenac sodium may be non-inferior to hydrocodone/APAP in treating pain after ESS with or without septoplasty in opioid naive patients without pre-existing pain conditions. Further studies with larger samples are warranted to investigate the potential superiority of diclofenac to hydrocodone/APAP in certain patients after ESS and septoplasty.Cancer cells survive by relying on oxidative stress defense against the accumulation of reactive oxygen species (ROS) during tumor formation. ROS-sensitive TRPA1 ion channels are overexpressed in breast cancer cells and induce a large influx of Ca2+ which upregulates the anti-apoptotic pathway to lead breast cancer cells to produce oxidative stress defense and enhance the resistance to ROS related chemotherapy. Targeting and inhibiting the TRPA1 ion channels are critical for breaking down the oxidative stress defense system and overcoming cellular resistance. Here, near-infrared (NIR) light-responsive conjugated polymer nanoparticles are designed and prepared to promote apoptosis of breast cancer cells, reduce cell drug resistance and suppress tumor growth through the remote and precise regulation of TRPA1 ion channels. Upon 808 nm laser irradiation, the nanoparticles block the formation of Ca2+ /CaM complex and regulate the content of MCL-1 protein. Especially, the nanoparticles overcome drug resistance of cancer cells, therefore accelerating apoptosis of cancer cells and suppressing tumor growth in mice. Compared with carboplatin, the volume of tumor induced by NPs-H decreases by 54.1%. This work provides a strategy to disrupt the oxidative stress defense system and downregulate the antiapoptotic signaling pathway in cancer cells.Conventional formulation strategies for hydrophobic small-molecule drug products frequently include mechanical milling to decrease active pharmaceutical ingredient (API) crystal size and subsequent granulation processes to produce an easily handled powder. A hydrogel-templated anti-solvent crystallization method is presented for the facile fabrication of microparticles containing dispersed nanocrystals of poorly soluble API. Direct crystallization within a porous hydrogel particle template yields core-shell structures in which the hydrogel core containing API nanocrystals is encased by a crystalline API shell. The process of controllable loading (up to 64% w/w) is demonstrated, and tailored dissolution profiles are achieved by simply altering the template particle size. API release is well described by a shrinking core model. Overall, the approach is a simple, scalable and potentially generalizable method that enables novel means of independently controlling both API crystallization and excipient characteristics, offering a "designer" drug particle system.Mimicking the multi-scale highly ordered hydroxyapatite (HAp) nanocrystal structure of the natural tooth enamel remains a great challenge. Herein, a bottom-up step-by-step strategy is developed using extrusion-based 3D printing technology to achieve a high-precision dental crown with multi-scale highly ordered HAp structure. In this study, hybrid resin-based composites (RBCs) with "supergravity +" HAp nanorods can be printed smoothly via direct ink writing (DIW) 3D printing, induced by shear force through a custom-built nozzle with a gradually shrinking channel. The theoretical simulation results of finite element method are consistent with the experimental results. The HAp nanorods are first highly oriented along a programmable printing direction in a single printed fiber, then arranged in a layer by adjusting the printing path, and finally 3D printed into a highly ordered and complex crown structure. The printed samples with criss-crossed layers by interrupting crack propagation exhibit a flexural strength of 134.