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‘Invisible actors’-How poor methodology reporting compromises mouse models of oncology: A cross-sectional survey.

The laboratory mouse is a key player in preclinical oncology research. However, emphasis of techniques reporting at the expense of critical animal-related detail compromises research integrity, animal welfare, and, ultimately, the translation potential of mouse-based oncology models. To evaluate current reporting practices, we performed a cross-sectional survey of 400 preclinical oncology studies using mouse solid-tumour models. Articles published in 2020 were selected from 20 journals that specifically endorsed the ARRIVE (Animal Research: Reporting of In Vivo Experiments) preclinical reporting guidelines. We assessed reporting compliance for 22 items in five domains: ethical oversight assurance, animal signalment, husbandry, welfare, and euthanasia. Data were analysed using hierarchical generalised random-intercept models, clustered on journal. Overall, reporting of animal-related items was poor. Median compliance over all categories was 23%. There was little or no association between extent of reporting compliance and journal or journal impact factor. Age, sex, and source were reported most frequently, but verifiable strain information was reported for <10% of studies. Animal husbandry, housing environment, and welfare items were reported by <5% of studies. Fewer than one in four studies reported analgesia use, humane endpoints, or an identifiable method of euthanasia. Of concern was the poor documentation of ethical oversight information. Fewer than one in four provided verifiable approval information, and almost one in ten reported no information, or information that was demonstrably false. Mice are the "invisible actors" in preclinical oncology research. In spite of widespread endorsement of reporting guidelines, adherence to reporting guidelines on the part of authors is poor and journals fail to enforce guideline reporting standards. In particular, the inadequate reporting of key animal-related items severely restricts the utility and translation potential of mouse models, and results in research waste. Both investigators and journals have the ethical responsibility to ensure animals are not wasted in uninformative research.

The surgical strategy of hormonally active primary cardiac paraganglioma sarcoma: A case report.

Cardiac paraganglioma is a kind of rare neuroendocrine tumor characterized by the persistent secretion of catecholamines. Under excessive exposure of catecholamines, some atypical symptoms are presented, including hypertension, arrhythmias, and headache. The case of surgical treatment of a 28-year-old woman with primary cardiac paraganglioma is presented for experience sharing and surgical skill improvements.

Targeting α7 nicotinic acetylcholine receptors for chronic pain.

Despite rapid advances in the field of chronic pain, it remains extremely challenging in the clinic. Pain treatment strategies have not improved for decades as opioids remain the main prescribed drugs for chronic pain management. However, long-term use of opioids often leads to detrimental side effects. Therefore, uncovering the mechanisms underlying the development and maintenance of chronic pain may aid the discovery of novel therapeutics to benefit patients with chronic pain. Substantial evidence indicates downregulation of α7 nicotinic acetylcholine receptors (α7 nAChR) in the sciatic nerve, dorsal root ganglia, and spinal cord dorsal horn in rodent models of chronic pain. Moreover, our recent study and results from other laboratories demonstrate that potentiation of α7 nAChR attenuates pain behaviors in various murine models of chronic pain. This review summarized and discussed the preclinical evidence demonstrating the therapeutic potential of α7 nAChR agonists and allosteric modulators in chronic pain. This evidence indicates that potentiation of α7 nAChR is beneficial in chronic pain, mostly by alleviating neuroinflammation. Overall, α7 nAChR-based therapy for chronic pain is an area with great promise, but more research regarding its detailed mechanisms is warranted.

Contrast Medium Use in Computed Tomography for Patients Presenting with Headache: 4-year Retrospective Two-Center Study in Central and Western Regions of Ghana.

Contrast medium (CM) administration during computed tomography (CT) enhances the accuracy in the detection and interpretation of abnormalities. Evidence from literature also validate the essence of CM in imaging studies. CT, by virtue of its ubiquity, ease of use, speed, and lower financial footprint, is usually the first investigation in cases of headache. Through a multicenter retrospective analysis, we compared findings of contrast-enhanced CT (CECT) to noncontrast-enhanced CT (NCECT) head examinations among patients presenting with headache.

Validity and reliability of the Arabic version of the revised illness perception questionnaire for patients with hypertension.

Hypertension is one of the leading causes of morbidity and mortality in Saudi Arabia affecting 31.4% of the population. The Illness Perception Questionnaire-Revised (IPQ-R) is a validated and reliable tool for assessing the perception of hypertension among patients. This cross-sectional study aimed to translate the Revised Illness Perception Questionnaire (IPQ-R) into Arabic and validate it among Arabic patients with hypertension from the outpatient departments of the Prince Sattam University Hospital and King Khalid Hospital (KKH) in Al-Kharj City in the Kingdom of Saudi Arabia.

Superficial Venous-Associated Inflammation from Direct IV Administration of RRx-001 in Rats.

RRx-001 is a small molecule NLRP3 inflammasome inhibitor with anti-CD47 and antiangiogenic/vascular normalization properties in a Phase 3 clinical trial that has been designated as a drug-device combination by the FDA. In the Phase 1 first-in-man dose escalation clinical trial, where RRx-001 was given by direct intravenous (IV) infusion, the main adverse event was a sterile painful infusion phlebitis (IP). Less pain was experienced when RRx-001 was infused at a slower rate over multiple hours which was impractical on an outpatient basis. In Phase 2, for reasons of convenience and safety, RRx-001 was co-administered with an aliquot of autologous blood from an device called the eLOOP on the premise that RRx-001 binds to hemoglobin on red blood cells (RBCs), making it unavailable to directly interact with venous nociceptors. Phlebitis has the potential to progress to deep venous thrombosis or septic thrombophlebitis or post-thrombotic syndrome in hypercoagulable and immunosuppressed cancer patients. In this 13-week toxicology study of once weekly IV RRx-001 administration to Wistar Han rats followed by a recovery period of 28 days. The main observed toxicity was a significant inflammatory response in the vein wall, consistent with superficial venous thrombosis observed in man. Due to this development, direct IV infusion of RRx-001 is relatively contraindicated in favor of co-administration with autologous blood.

Single ultrasound-guided thoracic paravertebral block with a large volume of anesthetic for microwave ablation of lung tumors.

To compare single ultrasound-guided thoracic paravertebral block (TPVB) using a large volume of anesthetic with local anesthesia (LA) in computed tomography (CT)-guided pulmonary microwave ablation.

Baricitinib is potentially effective in the treatment of refractory livedoid vasculopathy.

Livedoid vasculopathy is a rare, chronic, and recurrent disease with limited effective treatments. Its etiopathogenesis remains incompletely understood. Baricitinib, a selective Janus kinase 1 and 2 inhibitor, has been used to treat rheumatoid arthritis and could reduce the disease severity in patients with livedoid vasculopathy.

The Woman Who Cried Pain: Do Sex-Based Disparities Still Exist in the Experience and Treatment of Pain?

Over twenty years have passed since published "The Girl Who Cried Pain: A Bias Against Women in the Treatment of Pain." This article revisits the conclusions drawn in that piece and explores what we have learned in the last two decades regarding the experience of men and women who have chronic pain and whether women continue to be treated less aggressively for their pain than men.

Dorsal root ganglion stimulation produces differential effects on action potential propagation across a population of biophysically distinct C-neurons.

Dorsal root ganglion stimulation (DRGS) is a neurostimulation therapy used to manage chronic pain that does not respond to conventional therapies. Unfortunately, not all patients receive sufficient pain relief from DRGS, leaving them with few other treatment options. Presently, our understanding of the mechanisms of action of DRGS is incomplete, preventing us from determining why some patients do not receive analgesia from the therapy. One hypothesis suggests that DRGS augments the filtering of action potentials (APs) at the T-junction of nociceptive C-neurons. To test this hypothesis, we utilized a computational modeling approach in which we developed a population of one thousand biophysically distinct C-neuron models which each produced electrophysiological characteristics (e.g., AP height, AP duration) reported in previous experimental studies. We used this population of model C-neurons to study how morphological and electrophysiological characteristics affected the propagation of APs through the T-junction. We found that trains of APs can propagate through the T-junction in the orthodromic direction at a higher frequency than in the antidromic direction due to the decrease in axonal diameter from the peripheral to spinal axon. Including slow outward conductances in the axonal compartments near the T-junction reduced following frequencies to ranges measured experimentally. We next used the population of C-neuron models to investigate how DRGS affected the orthodromic propagation of APs through the T-junction. Our data suggest that suprathreshold DRGS augmented the filtering of APs at the T-junction of some model C-neurons while increasing the activity of other model C-neurons. However, the stimulus pulse amplitudes required to induce activity in C-neurons (i.e., several mA) fell outside the range of stimulation pulse amplitudes used clinically (i.e., typically ≤1 mA). Furthermore, our data suggest that somatic GABA currents activated directly or indirectly by the DRGS pulse may produce diverse effects on orthodromic AP propagation in C-neurons. These data suggest DRGS may produce differential effects across a population of C-neurons and indicate that understanding how inherent biological variability affects a neuron's response to therapeutic electrical stimulation may be helpful in understanding its mechanisms of action.

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