Peripheral Sensitization Increases Opioid Receptor Expression And Activation By Crotalphine In Rats

Inflammation enhances the peripheral analgesic efficacy of opioid drugs, but the mechanisms involved in this phenomenon have not been fully elucidated. Crotalphine (CRP), a peptide that was first isolated from South American rattlesnake C.d. terrificus venom, induces a potent and long-lasting anti-nociceptive effect that is mediated by the activation of peripheral opioid receptors. Because the high efficacy of CRP is only observed in the presence of inflammation, we aimed to elucidate the mechanisms involved in the CRP anti-nociceptive effect induced by inflammation. Using real-time RT-PCR, western blot analysis and ELISA assays, we demonstrate that the intraplantar injection of prostaglandin E2 (PGE2) increases the mRNA and protein levels of the μ- and κ-opioid receptors in the dorsal root ganglia (DRG) and paw tissue of rats within 3 h of the injection. Using conformation state-sensitive antibodies that recognize activated opioid receptors, we show that PGE 2, alone does not increase the activation of these opioid receptors but that in the presence of PGE2, the activation of specific opioid receptors by CRP and selective μ- and κ-opioid receptor agonists (positive controls) increases. Furthermore, PGE2 down-regulated the expression and activation of the δ-opioid receptor. CRP increased the level of activated mitogen-activated protein kinases in cultured DRG neurons, and this increase was dependent on the activation of protein kinase Cζ. This CRP effect was much more prominent when the cells were pretreated with PGE 2. These results indicate that the expression and activation of peripheral opioid receptors by opioid-like drugs can be up- or down-regulated in the presence of an acute injury and that acute tissue injury enhances the efficacy of peripheral opioids. © 2014 Zambelli et al.93Stein, C., Peripheral mechanisms of opioid analgesia (1993) Anesth Analg, 76, pp. 182-191Obara, I., Parkitna, J.R., Korostynski, M., Makuch, W., Kaminska, D., Local peripheral opioid effects and expression of opioid genes in the spinal cord and dorsal root ganglia in neuropathic and inflammatory pain (2009) Pain, 141, pp. 283-291Puehler, W., Zollner, C., Brack, A., Shaqura, M.A., Krause, H., Schafer, M., Stein, C., Rapid upregulation of mu opioid receptor mRNA in dorsal root ganglia in response to peripheral inflammation depends on neuronal conduction (2004) Neuroscience, 129 (2), pp. 473-479. , DOI 10.1016/j.neuroscience.2004.06.086, PII S030645220400627XMaekawa, K., Minami, M., Masuda, T., Satoh, M., Expression of 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Implementing a Prison Medicaid Enrollment Program for Inmates with a Community Inpatient Hospitalization

In 2011, North Carolina (NC) created a program to facilitate Medicaid enrollment for state prisoners experiencing community inpatient hospitalization during their incarceration. The program, which has been described as a model for prison systems nationwide, has saved the NC prison system approximately $10 million annually in hospitalization costs and has potential to increase prisoners’ access to Medicaid benefits as they return to their communities. This study aims to describe the history of NC’s Prison-Based Medicaid Enrollment Assistance Program (PBMEAP), its structure and processes, and program personnel’s perspectives on the challenges and facilitators of program implementation. We conducted semi-structured interviews and a focus group with PBMEAP personnel including two administrative leaders, two “Medicaid Facilitators,” and ten social workers. Seven major findings emerged: 1) state legislation was required to bring the program into existence; 2) the legislation was prompted by projected cost savings; 3) program development required close collaboration between the prison system and state Medicaid office; 4) technology and data sharing played key roles in identifying inmates who previously qualified for Medicaid and would likely qualify if hospitalized; 5) a small number of new staff were sufficient to make the program scalable; 6) inmates generally cooperated in filling out Medicaid applications, and their cooperation was encouraged when social workers explained possible benefits of receiving Medicaid after release; and 7) the most prominent program challenges centered around interaction with county Departments of Social Services, which were responsible for processing applications. Our findings could be instructive to both Medicaid non-expansion and expansion states that have either implemented similar programs or are considering implementing prison Medicaid enrollment programs in the future

Symptomatic Sinus Node Disease: Natural History After Permanent Ventricular Pacing *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75403/1/j.1540-8159.1979.tb03650.x.pd

Medicaid Enrollment among Prison Inmates in a Non-expansion State: Exploring Predisposing, Enabling, and Need Factors Related to Enrollment Pre-incarceration and Post-Release

Prison inmates suffer from a heavy burden of physical and mental health problems and have considerable need for healthcare and coverage after prison release. The Affordable Care Act may have increased Medicaid access for some of those who need coverage in Medicaid expansion states, but inmates in non-expansion states still have high need for Medicaid coverage and face unique barriers to enrollment. We sought to explore barriers and facilitators to Medicaid enrollment among prison inmates in a non-expansion state. We conducted qualitative interviews with 20 recently hospitalized male prison inmates who had been approached by a prison social worker due to probable Medicaid eligibility, as determined by the inmates’ financial status, health, and past Medicaid enrollment. Interviews were transcribed verbatim and analyzed using a codebook with both thematic and interpretive codes. Coded interview text was then analyzed to identify predisposing, enabling, and need factors related to participants’ Medicaid enrollment prior to prison and intentions to enroll after release. Study participants’ median age, years incarcerated at the time of the interview, and projected remaining sentence length were 50, 4, and 2 years, respectively. Participants were categorized into three sub-groups based on their self-reported experience with Medicaid_ (1) those who never applied for Medicaid before prison (n = 6); (2) those who unsuccessfully attempted to enroll in Medicaid before prison (n = 3); and (3) those who enrolled in Medicaid before prison (n = 11). The six participants who had never applied to Medicaid before their incarceration did not hold strong attitudes about Medicaid and mostly had little need for Medicaid due to being generally healthy or having coverage available from other sources such as the Veteran’s Administration. However, one inmate who had never applied for Medicaid struggled considerably to access mental healthcare due to lapses in employer-based health coverage and attributed his incarceration to this unmet need for treatment. Three inmates with high medical need had their Medicaid applications rejected at least once pre-incarceration, resulting in periods without health coverage that led to worsening health and financial hardship for two of them. Eleven inmates with high medical need enrolled in Medicaid without difficulty prior to their incarceration, largely due to enabling factors in the form of assistance with the application by their local Department of Social Services or Social Security Administration, their mothers, medical providers, or prison personnel during a prior incarceration. Nearly all inmates acknowledged that they would need health coverage after release from prison, and more than half reported that they would need to enroll in Medicaid to gain healthcare coverage following their release. Although more population-based assessments are necessary, our findings suggest that greater assistance with Medicaid enrollment may be a key factor so that people in the criminal justice system who qualify for Medicaid—and other social safety net programs—may gain their rightful access to these benefits. Such access may benefit not only the individuals themselves but also the communities to which they return

An Experimental Investigation of Colonel Blotto Games

"This article examines behavior in the two-player, constant-sum Colonel Blotto game with asymmetric resources in which players maximize the expected number of battlefields won. The experimental results support all major theoretical predictions. In the auction treatment, where winning a battlefield is deterministic, disadvantaged players use a 'guerilla warfare' strategy which stochastically allocates zero resources to a subset of battlefields. Advantaged players employ a 'stochastic complete coverage' strategy, allocating random, but positive, resource levels across the battlefields. In the lottery treatment, where winning a battlefield is probabilistic, both players divide their resources equally across all battlefields." (author's abstract)"Dieser Artikel untersucht das Verhalten von Individuen in einem 'constant-sum Colonel Blotto'-Spiel zwischen zwei Spielern, bei dem die Spieler mit unterschiedlichen Ressourcen ausgestattet sind und die erwartete Anzahl gewonnener Schlachtfelder maximieren. Die experimentellen Ergebnisse bestätigen alle wichtigen theoretischen Vorhersagen. Im Durchgang, in dem wie in einer Auktion der Sieg in einem Schlachtfeld deterministisch ist, wenden die Spieler, die sich im Nachteil befinden, eine 'Guerillataktik' an, und verteilen ihre Ressourcen stochastisch auf eine Teilmenge der Schlachtfelder. Spieler mit einem Vorteil verwenden eine Strategie der 'stochastischen vollständigen Abdeckung', indem sie zufällig eine positive Ressourcenmenge auf allen Schlachtfeldern positionieren. Im Durchgang, in dem sich der Gewinn eines Schlachtfeldes probabilistisch wie in einer Lotterie bestimmt, teilen beide Spieler ihre Ressourcen gleichmäßig auf alle Schlachtfelder auf." (Autorenreferat

Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r’s ≥ 0.35; P’s < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself

Quantum mechanics: Myths and facts

A common understanding of quantum mechanics (QM) among students and practical users is often plagued by a number of "myths", that is, widely accepted claims on which there is not really a general consensus among experts in foundations of QM. These myths include wave-particle duality, time-energy uncertainty relation, fundamental randomness, the absence of measurement-independent reality, locality of QM, nonlocality of QM, the existence of well-defined relativistic QM, the claims that quantum field theory (QFT) solves the problems of relativistic QM or that QFT is a theory of particles, as well as myths on black-hole entropy. The fact is that the existence of various theoretical and interpretational ambiguities underlying these myths does not yet allow us to accept them as proven facts. I review the main arguments and counterarguments lying behind these myths and conclude that QM is still a not-yet-completely-understood theory open to further fundamental research.Comment: 51 pages, pedagogic review, revised, new references, to appear in Found. Phy

Key questions in marine mammal bioenergetics

Bioenergetic approaches are increasingly used to understand how marine mammal populations could be affected by a changing and disturbed aquatic environment. There remain considerable gaps in our knowledge of marine mammal bioenergetics, which hinder the application of bioenergetic studies to inform policy decisions. We conducted a priority-setting exercise to identify high-priority unanswered questions in marine mammal bioenergetics, with an emphasis on questions relevant to conservation and management. Electronic communication and a virtual workshop were used to solicit and collate potential research questions from the marine mammal bioenergetic community. From a final list of 39 questions, 11 were identified as ‘key’ questions because they received votes from at least 50% of survey participants. Key questions included those related to energy intake (prey landscapes, exposure to human activities) and expenditure (field metabolic rate, exposure to human activities, lactation, time-activity budgets), energy allocation priorities, metrics of body condition and relationships with survival and reproductive success and extrapolation of data from one species to another. Existing tools to address key questions include labelled water, animal-borne sensors, mark-resight data from long-term research programs, environmental DNA and unmanned vehicles. Further validation of existing approaches and development of new methodologies are needed to comprehensively address some key questions, particularly for cetaceans. The identification of these key questions can provide a guiding framework to set research priorities, which ultimately may yield more accurate information to inform policies and better conserve marine mammal populations

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012