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Handheld ultrasound-guided cannulation of difficult hemodialysis arteriovenous access: A randomized controlled trial.

Cannulation of complex arteriovenous fistula (AVF) or graft (AVG) frequently poses challenges to renal nursing practice. Ultrasound (US) guidance on visualizing central and peripheral venous access has been widely adopted in nephrology, reducing vascular intervention complications. Renal nurses could acquire this point-of-care technique to increase the successful cannulation rate while facilitating confidence build-up during practice. We aim to evaluate the use of handheld US on difficult AVF/AVG cannulation in a hospital-based dialysis unit.

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Green light exposure elicits anti-inflammation, endogenous opioid release and dampens synaptic potentiation to relieve post-surgical pain.

Light therapy improves multiple conditions such as seasonal affective disorders, circadian rhythm dysregulations, and neurodegenerative diseases. However, little is known about its potential benefits in pain management. While current pharmacologic methods are effective in many cases, the associated side effects can limit their use. Non-pharmacological methods would minimize drug dependence, facilitating a reduction of the opioid burden. Green light therapy has been shown to be effective in reducing chronic pain in humans and rodents. However, its underlying mechanisms remain incompletely defined. In this study, we demonstrate that green light exposure reduced post-surgical hypersensitivity in rats. Moreover, this therapy potentiated the antinociceptive effects of morphine and ibuprofen on mechanical allodynia in male rats. Importantly, in female rats, GLED potentiated the antinociceptive effects of morphine but did not affect that of ibuprofen. We showed that green light increases endogenous opioid levels while lessening synaptic plasticity and neuroinflammation. Importantly, this study reveals new insights into how light exposure can affect neuroinflammation and plasticity in both genders. Clinical translation of these results could provide patients with improved pain control and decrease opioid consumption. Given the noninvasive nature of green light, this innovative therapy would be readily implementable in hospitals. PERSPECTIVE: This study provides a potential additional therapy to decrease post-surgical pain. Given the safety, availability, and the efficacy of green light therapy, there is a significant potential for advancing the green light therapy to clinical trials and eventual translation to clinical settings.

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Systemic administration of dorsomorphin relieves inflammatory nociception in the mouse formalin test.

Inflammatory pain is the most important clinical symptom of inflammatory diseases. Despite intensive research into inflammatory pain mechanisms, the majority of analgesics available are based on mechanistic classes of compounds that have been known for many years, as a result, inflammatory pain control remains a challenge for drug design in the context of clinically unmet needs in terms of safety and efficacy. A growing literature supports that pro-inflammatory cytokine signaling plays a crucial role in the development of inflammatory pain. Modulation of the pro-inflammatory cytokine may hold the key to improved pain management. Previous studies have reported that dorsomorphin played key roles in inflammation. But the role of dorsomorphin in the formalin-induced inflammatory nociception in mice has never been reported. Here, we report a new function of dorsomorphin which can inhibit formalin-induced inflammatory nociception in mice. The antinociceptive effect of dorsomorphin mainly depended on inhibiting the p38 MAPK/c-fos signaling and regulating inflammatory mediators.

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Ketamine in Critically Ill Patients: Use, Perceptions, and Potential Barriers.

To evaluate practitioner use of ketamine and identify potential barriers to use in acutely and critically ill patients. To compare characteristics, beliefs, and practices of ketamine frequent users and non-users. An online survey developed by members of the Society of Critical Care Medicine (SCCM) Clinical Pharmacy and Pharmacology Section was distributed to physician, pharmacist, nurse practitioner, physician assistant and nurse members of SCCM. The online survey queried SCCM members on self-reported practices regarding ketamine use and potential barriers in acute and critically ill patients. Respondents, 341 analyzed, were mostly adult physicians, practicing in the United States at academic medical centers. Clinicians were comfortable or very comfortable using ketamine to facilitate intubation (80.0%), for analgesia (77.9%), procedural sedation (79.4%), continuous ICU sedation (65.8%), dressing changes (62.4%), or for asthma exacerbation and status epilepticus (58.8% and 40.4%). Clinicians were least comfortable with ketamine use for alcohol withdrawal and opioid detoxification (24.7% and 23.2%). Most respondents reported "never" or "infrequently" using ketamine preferentially for continuous IV analgesia (55.6%) or sedation (61%). Responses were mixed across dosing ranges and duration. The most common barriers to ketamine use were adverse effects (42.6%), other practitioners not routinely using the medication (41.5%), lack of evidence (33.5%), lack of familiarity (33.1%), and hospital/institutional policy guiding the indication for use (32.3%). Although most critical care practitioners report feeling comfortable using ketamine, there are many inconsistencies in practice regarding dose, duration, and reasons to avoid or limit ketamine use. Further educational tools may be targeted at practitioners to improve appropriate ketamine use.

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Edmonton Classification System for Cancer Pain: Comparison of Pain Classification Features and Pain Intensity across Diverse Palliative Care Settings in Canada.

The goal of the Edmonton Classification System for Cancer Pain (ECS-CP) is to create an international classification system for cancer pain. Previous studies reinforce the need for standardized training to ensure consistency across assessors. There is no universally accepted classification for neuropathic pain. Our primary objective was to describe the prevalence of ECS-CP features in a diverse sample of advanced cancer patients, using assessors with standardized training. The secondary objectives were to: (1) determine the prevalence of neuropathic pain using the Neuropathic Pain Special Interest Group (NeuPSIG) criteria and (2) examine the relationship between specific predictors: ECS-CP features, age, Palliative Performance Scale, Morphine Equivalent Daily Dose (MEDD), setting, and pain intensity; and neuropathic pain. A total of 1050 adult patients with advanced cancer were recruited from 11 Canadian sites. A clinician completed the ECS-CP and NeuPSIG criteria, and collected additional information including demographics and pain intensity (now). All assessors received standardized training. Of 1050 evaluable patients, 910 (87%) had cancer pain: nociceptive ( = 626; 68.8%); neuropathic ( = 227; 24.9%); incident ( = 329; 36.2%); psychological distress ( = 209; 23%); addictive behavior ( = 51; 5.6%); and normal cognition ( = 639; 70.2%). The frequencies of ECS-CP features and pain intensity scores varied across sites and settings, with more acute settings having higher frequencies of complex pain features. The overall frequency of neuropathic pain was 24.9%, ranging from 11% (hospices) to 34.2% (palliative outpatient clinic) across settings. Multivariate logistic regression analysis revealed that age <60 years, MEDD ≥19 mg, pain intensity ≥7/10, and incident pain were significant independent predictors of neuropathic pain ( < 0.05). The ECS-CP was able to detect salient pain features across settings. Furthermore, the frequencies of neuropathic pain utilizing the NeuPSIG criteria fits within the lower-end of literature estimates (13%-40%). Further research is warranted to validate the NeuPSIG criteria in cancer pain.

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The relationship between trust and outcomes during physical therapy care for chronic low back pain.

Enhancing the therapeutic alliance has been associated with improved outcomes for patients with chronic low back pain (CLBP). Qualitatively trust has been described to be part of the therapeutic alliance, but it has not been measured quantitatively within the physical therapy literature.

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A Modified Murine Heterotopic Heart Transplant Protocol Matching Contemporary Standards of Aseptic Technique, Anesthesia, and Analgesia.

The development of experimental models of cardiac transplantation in animals has contributed to many advances in the fields of immunology and solid organ transplantation. While the heterotopic vascularized murine cardiac transplantation model was initially utilized in studies of graft rejection using combinations of mismatched inbred mouse strains, access to genetically modified strains and therapeutic modalities can provide powerful new preclinical insights. Fundamentally, the surgical methodology for this technique has not changed since its development, especially with respect to important factors such as aseptic technique, anesthesia, and analgesia, which make material impacts on postsurgical morbidity and mortality. Additionally, improvements in perioperative management are expected to provide improvements in both animal welfare and experimental outcomes. This paper reports upon a protocol developed in collaboration with a subject matter expert in veterinary anesthesia and describes the surgical technique with an emphasis on perioperative management. Additionally, we discuss the implications of these refinements and provide details on troubleshooting critical surgical steps for this procedure.

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Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies.

Management of chronic pain remains challenging to this day, and current treatments are associated with adverse effects, including tolerance and addiction. Chronic neuropathic pain results from lesions or diseases in the somatosensory system. To investigate potential therapies with reduced side effects, animal pain models are the gold standard in preclinical studies. Therefore, well-characterized and well-described models are crucial for the development and validation of innovative therapies. Partial ligation of the sciatic nerve (pSNL) is a procedure that induces chronic neuropathic pain in mice, characterized by mechanical and thermal hypersensitivity, ongoing pain, and changes in limb temperature, making this model a great fit to study neuropathic pain preclinically. pSNL is an advantageous model to study neuropathic pain as it reproduces many symptoms observed in humans with neuropathic pain. Furthermore, the surgical procedure is relatively fast and straightforward to perform. Unilateral pSNL of one limb allows for comparison between the ipsilateral and contralateral paws, as well as evaluation of central sensitization. To induce chronic neuropathic hypersensitivity, a 9-0 non-absorbable nylon thread is used to ligate the dorsal third of the sciatic nerve. This article describes the surgical procedure and characterizes the development of chronic neuropathic pain through multiple commonly used behavioral tests. As a plethora of innovative therapies are now being investigated to treat chronic pain, this article provides crucial concepts for standardization and an accurate description of surgeries required to induce neuropathic pain.

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The Notch1/CD22 signaling axis disrupts Treg cell function in SARS-CoV2-associated multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcome were previously correlated with Notch4 expression on regulatory T (Treg) cells, here we show that the Treg cells in MIS-C are destabilized through a Notch1-dependent mechanism. Genetic analysis revealed that MIS-C patients were enriched in rare deleterious variants impacting inflammation and autoimmunity pathways, including dominant-negative mutations in the Notch1 regulators NUMB and NUMBL leading to Notch1 upregulation. Notch1 signaling in Treg cells induced CD22, leading to their destabilization in a mTORC1-dependent manner and to the promotion of systemic inflammation. These results establish a Notch1-CD22 signaling axis that disrupts Treg cell function in MIS-C and point to distinct immune checkpoints controlled by individual Treg cell Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.

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Preoperative Acute Sleep Deprivation Causes Postoperative Pain Hypersensitivity and Abnormal Cerebral Function.

Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients.

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