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Percutaneous coronary intervention from COURAGE to ISCHEMIA and beyond.

Multiple randomized clinical trials and observational studies in patients with chronic coronary artery disease have evaluated whether revascularization, in particular PCI, can reduce the incidence of future cardiovascular events and relieve angina. Perhaps the two most widely quoted trials are COURAGE and ISCHEMIA. In both trials revascularization did not reduce the incidence of cardiovascular death or non-fatal events. In both, revascularization did relieve angina, particularly in patients with severe pain. From the time of COURAGE to ISCHEMIA there were also multiple developments. In particular improved stent technology with second and third generation drug eluting stents in ISCHEMIA compared to bare metal stents in COURAGE. There was also the development of new methods to evaluate ischemia, in particular the potential surrogate fractional flow reserve. This period also saw improvement and maturation of coronary computed tomography angiography to assess coronary anatomy non-invasively. There was also greater emphasis on more intensive, guideline directed medical therapy to treat dyslipidemia and hypertension. There has also been greater recognition that not all angina is due to epicardial obstructive disease. Microvascular disease and coronary spasm are responsible for much of the symptom burden of ischemia. These data have led to a paradigm shift toward a more nuanced approach to treating stable ischemic heart disease, with less need for revascularization except in cases of particularly severe anatomic disease or unremitting symptoms while on optimal medial therapy. In recognition of the importance of disparities in cardiovascular health, it is crucial to implement preventive strategies with optimal medical therapy in the community.

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Fentanyl in the Labor Epidural Impacts the Results of Intrapartum and Postpartum Maternal and Neonatal Toxicology Tests.

A positive urine fentanyl toxicology test may have significant consequences for peripartum individuals, yet the extent to which fentanyl in a labor epidural may lead to such a positive test is poorly characterized.

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Activating PV-positive neurons in ventral thalamic reticular nucleus reduces pain sensitivity in mice.

Previous studies have demonstrated that thalamic reticular nucleus (TRN) and the sub-nuclei play important roles in pain sensation. Our previous findings showed that activating parvalbumin-positive (PV+) neurons in dorsal sector of TRN (dTRN) could reduce the pain threshold and consequently increase the pain sensitivity of mice. Recent studies have shown that activation of GABAergic projection of TRN to ventrobasal thalamus (VB) alleviated pathological pain. GABAergic neurons in TRN are mainly PV+ neurons. However, the exact roles of ventral TRN (vTRN) PV+ neurons in pain sensation remain unclear. In this study, the designer receptors exclusively activated by designer drugs (DREADD) method was used to activate the PV+ neurons in vTRN of PV-Cre transgenic mice, and the mechanical threshold and thermal latency were measured to investigate the regulatory effects of vTRN on pain sensitivity in mice. Thereafter, PV-Cre transgenic mice, conditional anterograde axonal tract tracing, and immunohistochemistry were used to investigate the distribution of PV+ neurons fibers in vTRN. The results showed that the activation of PV+ neurons in vTRN increased the mechanical threshold and thermal latency, which indicated reduction of pain sensitivity. The fibers of these neurons mainly projected to ventral posterolateral thalamic nucleus (VPL), ventral posteromedial thalamic nucleus (VPM), ventrolateral thalamic nucleus (VL), centrolateral thalamic nucleus (CL) and various other brain regions. These findings indicated that activation of PV+ neurons in the vTRN decreased pain sensitivity in mice, which provided additional evidence on the mechanisms of PV+ neurons of TRN in regulating neuralgia.

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Pott Luck.

A 10-year-old boy presented with headache, fever, left-sided ptosis, and right-sided forehead soft tissue swelling. There was no recent history of trauma or infection. The patient had a large, fluctuant mass on the right side of his forehead, upgaze restriction, left-sided ptosis, and bilateral optic disc edema. Magnetic resonance imaging of the brain showed a frontal bone extradural fluid collection superficial to the superior sagittal sinus in keeping with an epidural abscess. There were multiple venous thromboses and thickening and enhancement of the dura, compatible with meningitis. There was right sphenoid sinusitis. This patient had Potts puffy tumor, a rare diagnosis associated with a forehead swelling from frontal bone osteomyelitis and subperiosteal abscess. It is seen in the pediatric population in association with sinusitis or trauma. Antibiotics, anticoagulation, and acetazolamide were initiated, and the epidural abscess was evacuated. The symptoms and signs resolved with treatment.

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Feasibility and usefulness of brain imaging in catatonia.

Catatonia is a well characterized psychomotor syndrome that has recognizable motor, affective, behavioural and vegetative manifestations. Despite recent demonstration that catatonia is often associated with brain imaging abnormalities, there is currently no consensus or guidelines about the role of brain imaging. In this study, we assessed the feasibility of brain imaging in a series of patients with catatonia in a routine clinical setting and estimated the prevalence of clinically relevant radiological abnormalities. Sixty patients with catatonia were evaluated against sixty non-healthy controls subjects with headache. The MRI reports were reviewed, and MRI scans were also interpreted by neuroradiologists using a standardised MRI assessment. In this cohort, more than 85% of brain scans of patients with catatonia revealed abnormalities. The most frequently reported abnormalities in the catatonic group were white matter abnormalities (n = 44), followed by brain atrophy (n = 27). There was no evidence for significant differences in the frequency of abnormalities found in radiology reports and standardised neuroradiological assessments. The frequency of abnormalities was similar to that found in a population of non-healthy controls subjects with headache. This study shows that MRI is feasible in patients with catatonia and that brain imaging abnormalities are common findings in these patients. Most frequently, white matter abnormalities and diffuse brain atrophy are observed.

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Tolerogenic nanoparticles induce type II collagen-specific regulatory T cells and ameliorate osteoarthritis.

Local inflammation in the joint is considered to contribute to osteoarthritis (OA) progression. Here, we describe an immunomodulating nanoparticle for OA treatment. Intradermal injection of lipid nanoparticles (LNPs) loaded with type II collagen (Col II) and rapamycin (LNP-Col II-R) into OA mice effectively induced Col II-specific anti-inflammatory regulatory T cells, substantially increased anti-inflammatory cytokine expression, and reduced inflammatory immune cells and proinflammatory cytokine expression in the joints. Consequently, LNP-Col II-R injection inhibited chondrocyte apoptosis and cartilage matrix degradation and relieved pain, while injection of LNPs loaded with a control peptide and rapamycin did not induce these events. Adoptive transfer of CD4CD25 T cells isolated from LNP-Col II-R-injected mice suggested that T induced by LNP-Col II-R injection were likely responsible for the therapeutic effects. Collectively, this study suggests nanoparticle-mediated immunomodulation in the joint as a simple and effective treatment for OA.

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A Computerized Pharmacy Decision Support System (PDSS) for Headache Management: Observational Pilot Study.

Headaches are common and often lead patients to seek advice from a pharmacist and consequently self-medicate for relief. Computerized pharmacy decision support systems (PDSSs) may be a valuable resource for health care professionals, particularly for community pharmacists when counseling patients with headache, to guide treatment with over-the-counter medications and recognize patients who require urgent or specialist care.

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A Combination of 3D TOF MRA and FIESTA Predicts Surgery-Needed Primary Trigeminal Neuralgia and Specific Offending Vessels.

To investigate the predictive accuracy of three-dimension (3D) time-of-flight (TOF) MR angiography (MRA) and 3D Fast Imaging Employing Steady-state Acquisition (FIESTA) techniques in assessing neurovascular compression (NVC) with specific vessels in patients with primary trigeminal neuralgia (TN).

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Triptolide Alleviates Neuropathic Pain by Inhibiting the Activation of Microglial Toll-Like Receptor 3.

Current data indicates the incidence of neuropathic pain after surgical nerve injury is as high as 50%, thus representing a major problem for patients and for the medical system. Triptolide, a traditional Chinese herb, has anti-inflammatory effects on various neurodegenerative and neuroinflammatory diseases. This agent also reduces peripheral nerve injury-induced neuropathic pain, although the mechanism underlying this effect is still unknown.

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The effect of a combined indomethacin and levonorgestrel-releasing intrauterine system on short-term postplacement bleeding profile: a randomized proof-of-concept trial.

Long-acting reversible contraceptives, including hormonal levonorgestrel-releasing intrauterine systems, are the most effective methods of reversible contraception. However, unfavorable bleeding, particularly during the first months of use, is one of the most important reasons for discontinuation or avoidance. Minimizing this as early as possible would be highly beneficial. Nonsteroidal anti-inflammatory drugs inhibiting prostaglandin synthesis are known to reduce bleeding and pain at time of menses. A levonorgestrel-releasing intrauterine system has been developed with an additional reservoir containing indomethacin, designed to be released during the initial postplacement period.

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