Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

FUCK YOUR FEELINGS: THE AFFECTIVE WEAPONISATION OF FACTS AND REASON

This paper examines emerging trends in fact signaling: the performative invocation of the idea of Fact and Reason, distinct from the concrete presentation of evidence or reasoning, as a way to cultivate affective solidarity. Emblematic is the conservative influencer Ben Shapiro’s slogan, “facts don’t care about your feelings”: a paean to the mythological figure of emotionlessly objective truth which may then be weaponised against one’s enemies. Scholars are increasingly attentive to the ways in which what was once popularised as a ‘fake news’ epidemic is not simply a virulent strain of bad information in a fundamentally rational online ecosystem, but rather a broader crisis and transformation of what counts as truthful, trustworthy and authentic (e.g. Boler & Davis, 2018; also see Banet-Weiser, 2012). Our contribution emphasises the affective and habitual dimension of this phenomenon. Through a close analysis of Ben Shapiro’s content and personal brand, we show how the generic invocation of Fact and Reason cultivates a sense of affective attachment not defined by ideological consistency or, indeed, the actual practice of research or logical reasoning, but rather a particularly masculinised and adversarial ideal of Truth. The payoff is the reassurance and pleasure of a stable subject position from which one’s political opposition may be Othered with impunity. Facts may not care about your feelings, but insisting upon this fact is all about building a certain structure of feeling

A Fully Authenticated Diffie-Hellman Protocol and Its Application in WSNs

The secure authenticated key establishment between nodes in Wireless Sensor Networks (WSNs) has not been fully solved in the existing schemes. It\u27s a good idea to apply the Diffie-Hellman protocol to address it perfectly, but the existing authenticated Diffie-Hellman (ADH) protocols are not perfect because their authentication are partial or delayed. In this paper, we first present a concept of full authentication and propose a new fully authenticated Diffie-Hellman (FADH) prototype with light-certificate-based authentication. And then based on the theory of elliptic curve cryptography, we construct the TinyADH (Tiny Authenticated Diffie-Hellman) protocol with applying the FADH in WSNs. Compared with the existing similar solutions, TinyADH has lower communication overload, is easier to implement into existing standards, and more secure under equivalent computational complexity. The experimental results show that using this scheme for a successful key agreement between two nodes averagely takes about 54 seconds on TelosB. Moreover, the simulation results indicate that repeated key agreement can improve the secure connectivity rate. However, considering the cost performance ratio, it is advisable to take 2 runs of the negotiation

Effects of Exercise on Stress-induced Attenuation of Vaccination Responses in Mice

Studies suggest that exercise can improve vaccination responses in humans. Chronic stress can lead to immunosuppression, and there may be a role for exercise in augmenting immune responses. Purpose To investigate the effects of acute eccentric exercise (ECC) and voluntary wheel exercise training (VWR) on antibody and cell-mediated immune responses to vaccination in chronically stressed mice. We hypothesized that both ECC and VWR would attenuate chronic stress-induced reductions in vaccination responses. Methods Mice were randomized into four groups: control (CON), stress (S)-ECC, S-VWR, and S-sedentary (SED). Stressed groups received chronic restraint stress for 6 h·d-1, 5 d·wk-1 for 3 wk. After the first week of stress, S-ECC were exercised at 17 m·min-1 speed at -20% grade for 45 min on a treadmill and then intramuscularly injected with 100 μg of ovalbumin (OVA) and 200 μg of alum adjuvant. All other groups were also vaccinated at this time. Stress-VWR mice voluntarily ran on a wheel for the entire experiment. Plasma was collected before, and at 1, 2, and 4 wk postvaccination. Enzyme-linked immunosorbent assay was performed to analyze anti-OVA IgG and IgM antibodies. After 3 wk of chronic stress, all mice were injected with OVA into the ear to determine the delayed-type hypersensitivity. Results We found that chronic restraint stress significantly reduced body weight and caused adrenal hypertrophy. We also found both S-ECC and S-VWR groups had significantly elevated anti-OVA IgG (P \u3c 0.05), whereas no significant differences between the two exercise groups. Neither S-ECC nor S-VWR altered anti-OVA IgM or delayed-type hypersensitivity responses compared with S-SED group. Conclusions Acute eccentric exercise and voluntary exercise training alleviated the chronic stress-induced anti-OVA IgG reductions in vaccination responses

Raman Nanoparticle Probes for Antibody-based Protein Detection in Tissues

Surface-enhanced Raman scattering (SERS) nanoparticles are emerging as a new approach for optical detection of biomolecules. In a model assay in formalin-fixed paraffin-embedded (FFPE) prostate tissue sections, we detect prostate-specific antigen (PSA) using antibody (Ab) conjugated to composite organic–inorganic nanoparticles (COINs), and we use identical staining protocols to compare COIN-Ab and Alexa–Ab conjugates in adjacent tissue sections. Spectral analysis illustrates the fundamental difference between fluorescence and Raman signatures and accurately extracts COIN probe signals from background autofluorescence. Probe signals are used to generate images of PSA expression on the tissue, and quality measures are presented to characterize the performance of the COIN assay in comparison to Alexa. Staining accuracy (ability to correctly identify PSA expression in epithelial cells) is somewhat less for COIN than Alexa, which is attributed to an elevated false negative rate of the COIN. However, COIN provided signal intensities comparable to Alexa, and good intra-, inter-, and lot-to-lot consistencies. Overall, COIN and Alexa detection reagents possess similar performance with FFPE tissues, supporting the further development of Raman probes for this application. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 56:371–379, 2008

Spectral analysis of multiplex Raman probe signatures.

Raman nanoparticle probes are an emerging new class of optical labels for interrogation of physiological and pathological processes in bioassays, cells, and tissues. Although their unique emission signatures are ideal for multiplexing, the full potential of these probes has not been realized because conventional analysis methods are inadequate. We report a novel spectral fitting method that exploits the entire spectral signature to quantitatively extract individual probe signals from multiplex spectra. We evaluate the method in a series of multiplex assays using unconjugated and antibody-conjugated composite organic-inorganic nanoparticles (COINs). Results show sensitive multiplex detection of small signals (<2% of total signal) and similar detection limits in corresponding 4-plex and singlet plate binding assays. In a triplex assay on formalin-fixed human prostate tissue, two antibody-conjugated COINs and a conventional fluorophore are used to image expression of prostate-specific antigen, cytokeratin-18, and DNA. The spectral analysis method effectively removes tissue autofluorescence and other unknown background, allowing accurate and reproducible imaging (area under ROC curve 0.89 +/- 0.03) at subcellular spatial resolution. In all assay systems, the error attributable to spectral analysis constitutes <or=2% of total signal. The spectral fitting method provides (1) quantification of signals from multiplex spectra with overlapping peaks, (2) robust spot-by-spot removal of unknown background, (3) the opportunity to quantitatively assess the analysis error, (4) elimination of operator bias, and (5) simple automation appropriate for high-throughput analysis. The simple implementation and universal applicability of this approach significantly expands the potential of Raman probes for quantitative in vivo and ex vivo multiplex analysis

Activity and electrochemical properties: iron complexes of the anticancer drug triapine and its analogs

Triapine (3-AP), is an iron-binding ligand and anticancer drug that is an inhibitor of human ribonucleotide reductase (RNR). Inhibition of RNR by 3-AP results in the depletion of dNTP precursors of DNA, thereby selectively starving fast-replicating cancer cells of nucleotides for survival. The redox-active form of 3-AP directly responsible for inhibition of RNR is the Fe(II)(3-AP)2 complex. In this work, we synthesize 12 analogs of 3-AP, test their inhibition of RNR in vitro, and study the electronic properties of their iron complexes. The reduction and oxidation events of 3-AP iron complexes that are crucial for the inhibition of RNR are modeled with solution studies. We monitor the pH necessary to induce reduction in iron complexes of 3-AP analogs in a reducing environment, as well as the kinetics of oxidation in an oxidizing environment. The oxidation state of the complex is monitored using UV-Vis spectroscopy. Isoquinoline analogs of 3-AP favor the maintenance of the biologically active reduced complex and possess oxidation kinetics that allow redox cycling, consistent with their effective inhibition of RNR seen in our in vitro experiments. In contrast, methylation on the thiosemicarbazone secondary amine moiety of 3-AP produces analogs that form iron complexes with much higher redox potentials, that do not redox cycle, and are inactive against RNR in vitro. The catalytic subunit of human Ribonucleotide Reductase (RNR), contains a tyrosyl radical in the enzyme active site. Fe(II) complexes of 3-AP and its analogs can quench the radical and, subsequently, inactivate RNR. The potency of RNR inhibitors is highly dependent on the redox properties of the iron complexes, which can be tuned by ligand modifications. Complexes are found to be active within a narrow redox window imposed by the cellular environment

A novel method for detection of phosphorylation in single cells by surface enhanced Raman scattering (SERS) using composite organic-inorganic nanoparticles (COINs).

BACKGROUND:Detection of single cell epitopes has been a mainstay of immunophenotyping for over three decades, primarily using fluorescence techniques for quantitation. Fluorescence has broad overlapping spectra, limiting multiplexing abilities. METHODOLOGY/PRINCIPAL FINDINGS:To expand upon current detection systems, we developed a novel method for multi-color immuno-detection in single cells using "Composite Organic-Inorganic Nanoparticles" (COINs) Raman nanoparticles. COINs are Surface-Enhanced Raman Scattering (SERS) nanoparticles, with unique Raman spectra. To measure Raman spectra in single cells, we constructed an automated, compact, low noise and sensitive Raman microscopy device (Integrated Raman BioAnalyzer). Using this technology, we detected proteins expressed on the surface in single cells that distinguish T-cells among human blood cells. Finally, we measured intracellular phosphorylation of Stat1 (Y701) and Stat6 (Y641), with results comparable to flow cytometry. CONCLUSIONS/SIGNIFICANCE:Thus, we have demonstrated the practicality of applying COIN nanoparticles for measuring intracellular phosphorylation, offering new possibilities to expand on the current fluorescent technology used for immunoassays in single cells