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Influence of early-life adversity on responses to acute and chronic ethanol in female mice.

Stressful early-life experiences increase the risk of developing an alcohol use disorder. We had previously found that male C57BL/6J mice reared under limited bedding and nesting (LBN) conditions, a model of early-life adversity, escalate their ethanol intake in limited-access two-bottle choice (2BC) sessions faster than control (CTL)-reared counterparts when exposed to chronic intermittent ethanol (CIE) vapor inhalation. However, the alcohol consumption of female littermates was not affected by LBN or CIE. In the present study, we sought to determine whether this phenotype reflected a general insensitivity of female mice to the influence of early life stress on alcohol responses.

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Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy.

Arthritic diseases have attracted enormous scientific interest because of increased worldwide prevalence and represent a significant socioeconomic burden. Osteoarthritis (OA) is the most prevalent form of arthritis. It is a disorder of the diarthrodial joints, characterized by degeneration and loss of articular cartilage associated with adjacent subchondral bone changes. Chronic and unresolving inflammation has been identified as a critical factor driving joint degeneration and pain in OA. Despite numerous attempts at therapeutic intervention, no effective disease-modifying agents targeting OA inflammation are available to the patients. Inflammasomes are protein complexes known to play a critical role in the inflammatory pathology of several diseases, and their roles in OA pathogenesis have become evident over the last decade. In this sense, it is relevant to evaluate the vital role of inflammasomes as potential modulators of pathogenic features in OA. This review will provide an overview and perspectives on why understanding inflammasome activation is critical for identifying effective OA therapies. We elaborate on the contribution of extracellular mediators from the circulatory system and synovial fluid as well as intracellular activators within the synovial fibroblasts and articular chondrocytes toward invoking the inflammasome in OA. We further discuss the merits of emerging inflammasome targeting therapies and speculate on the potential strategies for inflammasome blockade for OA therapy.

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A Validated UHPLC-MS/MS Method for Determination of Nalbuphine in Human Plasma and Application for Pharmacokinetic Study of Patients Undergoing General Anesthesia.

Nalbuphine was a semisynthetic opioid analgesic widely used in the treatment of both acute and chronic pain. We developed and validated a rapid, simple and sensitive method by ultra-performance liquid chromatography-tandem mass spectrometry (MS/MS) for the simultaneous quantitation of nalbuphine in human plasma, and we reported the pharmacokinetic features of patients during general anesthesia for abdominal surgery. Sample separation was achieved on a Kinetex Phenyl-Hexyl column (50 × 2.1 mm, 1.7 μm) after simple protein precipitation with acetonitrile. The mobile phase was composed of acetonitrile and 3 mM of ammonium acetate aqueous solution with 0.1% formic acid. Gradient elution was used in 4.5 min with a flow rate of 0.5 mL/min at 40°C. MS detection using AB Sciex QTRAP 5500 mass spectrometer was characterized by electrospray ionization for positive ions in multiple reaction monitoring mode. Quantitative ion pairs were m/z 358.4 → 340.1 for nalbuphine and m/z 340.0 → 268.3 for nalmefene, which were used as the internal standard (IS). The calibration curves showed good linearity (r2>0.99) over concentration range of 0.1-500 ng/mL. The intra-and inter-batch precisions were within 10.67%, and accuracy ranged from 94.07 to 105.34%. The IS-normalized matrix factors were 1.02-1.03 with RSD% (≤5.82%). The recoveries ranged from 101.09 to 106.30%. In conclusion, a rapid, simple, sensitive and economical analytical method was developed and validated to detect the concentration in plasma samples obtained from patients receiving nalbuphine intravenous injection and was successfully applicated to human pharmacokinetic studies of nalbuphine.

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Low-Fluence Treatment with a novel fractionated 2,910 nm Fiber Laser improves Photodamage.

Facial rejuvenation by lasers that target water has been a mainstay of esthetic laser treatments for decades. Modern lasers more commonly treat a fraction of the skin surface using ablative, semi-ablative or non-ablative pulses.

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Multicentre observational study on multisystem inflammatory syndrome related to COVID-19 in Argentina.

The impact of the Pediatric Inflammatory Multisystem Syndrome temporally-associated with SARS-CoV-2 (PIMS-TS) in low and middle-income countries remains poorly understood. Our aim was to understand the characteristics and outcomes of PIMS-TS in Argentina.

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The Impact of Dorsal Root Ganglion Stimulation on Pain Levels and Functionality in Patients With Chronic Postsurgical Knee Pain.

Chronic postsurgical pain is a considerable source of disabling neuropathic pain. Rates of knee replacement surgeries are increasing, and many patients report chronic postsurgical pain in their wake. When conventional therapies prove ineffective, neuromodulation options such as dorsal root ganglion stimulation (DRGS) may be used. However, little is known about the effect of DRGS on improvements in quantitative functional outcome parameters.

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Pulse Intensity Effects of Burst and Tonic Spinal Cord Stimulation on Neural Responses to Brushing in Patients With Neuropathic Pain.

Tonic spinal cord stimulation (SCS) is accompanied by paresthesia in affected body regions. Comparatively, the absence of paresthesia with burst SCS suggests different involvement of the dorsal column system conveying afferent impulses from low-threshold mechanoreceptors. This study evaluated cortical activation changes during gentle brushing of a pain-free leg during four SCS pulse intensities to assess the effect of intensity on recruitment of dorsal column system fibers during burst and tonic SCS.

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Feasibility and Safety of High-Definition Infraslow Pink Noise Stimulation for Treating Chronic Tinnitus-A Randomized Placebo-Controlled Trial.

Tinnitus has been linked to activity and connectivity changes in the auditory cortex (AC), parahippocampus (PHC), and posterior cingulate cortex (PCC). Although previous studies have targeted these areas individually, no study has yet modulated them simultaneously. Furthermore, novel stimulation designs may be superior to traditional alternating or direct current stimulation. This pilot study investigated the feasibility and safety of a novel brain stimulation technique (high-definition transcranial infraslow pink noise stimulation [HD-tIPNS]) for treating chronic tinnitus targeting the AC, PHC, and PCC.

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Really just a little prick? A meta-analysis on adverse events in placebo control groups of seasonal influenza vaccination RCTs.

The Corona pandemic and ongoing mass vaccinations raise the question of the nocebo mechanisms involved. Since immunization is usually administered to healthy people as a preventive health measure, adverse events (AE) following immunization are less accepted and could contribute to vaccine hesitancy. Assuming that vaccinees experience nocebo responses, the aim of this meta-analysis was to investigate the effect sizes of solicited adverse events (or assumed reactogenicity) reported in placebo groups in RCTs on seasonal influenza vaccination.

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Systematic review and meta-analysis of ketamine-associated uropathy.

This systematic review and meta-analysis focused on the literature regarding ketamine-associated uropathy to summarise its clinical manifestations, the results of urological assessments, and current management.

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