Rejected

Superior vena cava (SVC) syndrome is a clinical entity with signs and symptoms resulting from obstruction of blood flow through the SVC. The resulting obstruction leads to edema in the upper body, including the head, neck, and upper extremities. Clinical signs and symptoms can include plethora, cyanosis, dyspnea, stridor, cough, and hoarseness, as well as more serious complications such as cerebral edema leading to headache, confusion, and coma. Here, we present an interesting case of a 66-year-old female, with a medical history of esophageal cancer in remission and thyroid cancer currently undergoing radiation therapy, who was admitted for facial and upper extremity swelling. The initial impression was of angioedema or an allergic reaction. Imaging studies showed thrombus in the SVC resulting in SVC syndrome. The patient was treated with heparin initially, with a plan for an interventional radiologist to perform catheter-guided thrombolysis. However, the patient became unstable and ended up requiring mechanical ventilation. The patient was eventually discharged on oral anticoagulants. This case was rare as the patient developed SVC syndrome from venous thrombosis in the absence of any external tumor compression or as a result of an intravascular catheter.

Late onset Wilson disease (WD) is a rare form of WD. WD has variability of clinical presentations from acute liver failure to chronic liver disease (CLD). The hepatic and neurological variants of WD have wider variations.

Open trigger finger release is generally performed in the operating room in an outpatient setting. Its complication rate widely varies between 1% and 43%. Our goal was to determine whether performing this surgery in the clinic is a safe and viable alternative to performing this surgery in the operating room.

Acetaminophen is a popular, universally used, over-the-counter pain medication contained in more than 600 different products and available in a plethora of dosage forms. Acetaminophen is an important adjunct to manage postoperative dental pain in combination with a nonsteroidal anti-inflammatory drug such as ibuprofen. For the treatment of more severe pain, acetaminophen is often formulated with non-opioid and opioid agents. Because of the accessibility of acetaminophen and its widespread use, dental practitioners need to be cognizant of any significant safety concerns that may be associated with this drug, including acetaminophen toxicity. This article discusses the history of acetaminophen, its pharmacology, metabolism, and toxicity, as well as strategies to help address some of the potential safety issues with this medication, including unintentional overdosing.

While pain is frequent manisfestation of several disease processes, chronic pain has been described as an established disorder with debilitating ramifications on health and lifestyle. The currently available analgesics for the treatment of chronic pain are often ineffective and accompanied by undesirable adverse effects, which invites for safer and more efficacious alternatives. Adenosine is a naturally-occurring purinergic nucleoside that is involved in cell signaling in multiple tissue types. Although the activation of adenosine receptors can affect nociceptive, inflammatory, and neuropathic pain states, the specific regulatory functions of its subtypes (A1, A2A, A2B and A3 receptors) are not fully understood. The aim of this work was to investigate the role played by different adenosine receptor ligands on inflammatory pain conditions. Inflammatory pain was induced by intra-plantar injection of Complete Freund's Adjuvant (CFA) into the left hindpaw of adult male Sprague Dawley rats. Von Frey filaments were applied to the mid-plantar aspect of the left hind paw using the "up-down" method to determine the CFA-induced mechanical allodynia (expressed as paw withdrawal threshold, PWT). Neither the A2A selective agonist CGS 21680 hydrochloride (0.1, 0.32 and 1 mg/kg) nor the A2B selective agonist BAY 60-6583 (0.1, 0.32 and 1 mg/kg) produced any significant reversal of the PWT. However, both the A1 selective agonist (±)-5'-Chloro-5'-deoxy-ENBA, and the A3 selective agonist 2-Cl-IB-MECA produced a significant reversal of the PWT at the highest dose of 1 mg/kg, suggesting antinociceptive effects of the A1 and A3 adenosine receptors. Co-administration of the selective antagonists of A1 and A3 receptors PSB36 (1 mg/ml) and MRS-3777 (1 mg/ml); respectively, significantly reduced the anti-nociceptive effects of both (±)-5'-Chloro-5'-deoxy-ENBA, and 2-Cl-IB-MECA (1 mg/kg) on PWT one hour post-drug administration. Both the A2A selective antagonist ZM 241385 and the A2B selective antagonist PSB 603 produced a significant reversal of the PWT at the highest dose of 1 mg/kg. In conclusion, A1, A2A, A2B and A3 adenosine receptors are involved in mediating inflammatory pain states, and represent promising targets for the treatment of chronic pain conditions.

Myofascial syndrome is a common cause of chronic musculoskeletal pain and is characterized by myofascial trigger points (MTPs). MTPs are clinically identified by palpation of a muscle or fascial taut band. Although pathophysiology of MTPs remains unclear, coincidence between them and muscle motor plate at the innervation zone (IZ) have been reported. The temporal muscle is related to headache and temporomandibular disorders and pain radiates from hyperalgesic points to distant areas symptomatic patients. Clinical reports usually describe four trigger points located in the temporal muscle and we aimed to identify anatomical correlation with muscle innervation.

Trigeminal neuralgia, a debilitating pain disorder affecting the trigeminal nerve distribution, is often treated through percutaneous procedures using the route of Härtel. Miscannulation and excessive attempts at traversing the foramen ovale can negatively affect surgical outcomes. Complications attributed to miscannulation include blindness, brainstem hematoma, temporal lobe hematoma, and carotid artery hemorrhage. Currently, there is disagreement regarding the best skin entry point for the percutaneous approach. However, identifying an optimum entry point for cannulation can decrease the number of attempts necessary for a successful cannulation and also decrease the amount of fluoroscopic radiation exposure for both the patient and the surgeon. Therefore, this cadaveric study assessed a total of 56 cadavers to identify the optimum skin entry point. Calvariae, brains, and trigeminal nerves were removed, and the foramina ovalae were exposed. A lumbar needle was inserted through each porous trigeminus and foramen ovale at varied angles. The cannulation procedure was "reversed" by inserting the needle from the interior of the cranium through the porous trigeminus, foramen ovale, and skin. The exit location of the needle relative to facial structures was assessed. The exit points from the facial skin, which would otherwise represent the optimal entry points for the percutaneous procedure, were recorded. The results of this study represent an improvement in the percutaneous approach for the management of trigeminal neuralgia.

Neuroinflammation contributes to several health conditions related to the central nervous system, such as Alzheimer's Disease and pain. Understanding the regulation of neuroinflammation is essential for discovering approaches to treat inflammation-related diseases. Previous studies demonstrated that the inhibition of Heat shock protein 90 (Hsp90) using 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) could reduce neuroinflammation. However, the contribution of Hsp90 isoforms, including Hsp90α, Hsp90β, glucose-regulated protein 94 (Grp94), and tumor necrosis factor type 1 (TRAP1), to inflammatory signaling remain poorly understood. This study aimed to determine the impact of selective inhibitors for Hsp90β on lipopolysaccharide (LPS)-induced inflammatory responses in microglial cells. A murine microglial cell line, BV-2 cells, were pretreated with selective inhibitors for Hsp90β for 1 hour, followed by the stimulation of LPS. The production of Nitric Oxide (NO) was measured using Griess Reagents, and qPCR was performed to detect the expression of tumor necrosis factor-alpha (TNF-α) and Interleukin-1 beta (IL-1β). In addition, the activation of the nuclear factor-κB (NF-κB) and Nrf2 were investigated. The impact of selected inhibitors on the activation of extracellular-signal-regulated kinases (ERK), p38 mitogen-activated protein kinases (p38 MAPK), and c-Jun-N-terminal kinases (JNK) was measured using Western Blots. We found that treatment with Hsp90β inhibitorsstrongly inhibited the production of NO, TNF-α, and IL-1β, and the activation of NF-κB, but showed a modest effect on Nrf2 activation. Additionally, the Hsp90β inhibitors also showed to inhibit the activation of ERK, but no effect on p38 and JNK activation. These findings demonstrate that Hsp90β plays a vital role in the LPS-induced neuroinflammation in microglial cells.

During diving, Weddell seals (Leptonychotes weddellii) experience repeated hypoxemia. To mediate hypoxic tissue damage, Weddell seals employ vasoconstriction favoring vital organs (e.g. brain, lung, adrenals) resulting in reduced oxygen delivery to visceral and peripheral tissues. Weddell seals therefore experience periods of local ischemia associated with vasoconstriction followed by reoxygenation and return of perfusion at the surface. Ischemia-reperfusion injury (IRI) is the expected result from reduced blood flow and localized hypoxia, followed by reoxygenation and reperfusion. A typical human response to IRI induces inflammation. We studied the inflammatory response of Weddell seals to determine whether its downregulation could be a mechanism by which seals avoid hypoxic and IRI injury. Weddell seal white blood cells (n=12) demonstrate a reduced immune reaction (mean ± stdev 247± 200 fold induction of IL-6 from baseline) compared to human monocytes (n=6 replicates, THP-1 cells 3091 ± 1126 fold IL-6 induction, t-test p<0.0001) when exposed to an inflammatory stimulus in vitro (10 ng/mL lipopolysaccharide). To evaluate species differences in gene pathways associated with the immune response, we conducted RNA-seq and identified distinct transcriptomic profiles between species. We next evaluated the inflammatory response of Weddell seal primary cells (monocytes and pulmonary endothelial cells) resulting from hypoxia and reoxygenation. By simulating this natural stressor, we aim to discover whether the response of immune cells is an important component of molecular protection against IRI inflammatory sequelae in diving seals.

Gut microbiota has been reported to protect from lung viral infection in animal models by stimulating type-I interferon signaling. Type-I interferons can have direct antiviral activity while also stimulating antibody-producing B cells. Antibodies against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV2) have been correlated to faster infection clearance and protection against reinfection. A specific 4-strain probiotic combination (Pediococcus acidilactici CECT7483 plus Lactoplantibacillus plantarum CECT7484, CECT7485 and CECT30292) was recently studied in a randomized, quadruple-blinded, placebo-controlled trial in 300 SARS-CoV2-infected, symptomatic ambulatory patients (NCT04517422). Study subjects did not receive corticosteroids or antivirals. Compared to placebo, probiotic intervention (2×10 cfu/day for 30 days) achieved faster symptom clearance and increased SARS-CoV2-specific immunoglobulins M and G (IgM and IgG). We hypothesize these effects could be related to increased type-I interferon signaling.