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The use of anthrax as a weapon of biological terrorism has moved from theory to reality in recent weeks. Following processing of a letter containing anthrax spores that had been mailed to a US senator, 5 cases of inhalational anthrax have occurred among postal workers employed at a major postal facility in Washington, DC. This report details the clinical presentation, diagnostic workup, and initial therapy of 2 of these patients. The clinical course is in some ways different from what has been described as the classic pattern for inhalational anthrax. One patient developed low-grade fever, chills, cough, and malaise 3 days prior to admission, and then progressive dyspnea and cough productive of blood-tinged sputum on the day of admission. The other patient developed progressively worsening headache of 3 days' duration, along with nausea, chills, and night sweats, but no respiratory symptoms, on the day of admission. Both patients had abnormal findings on chest radiographs. Non-contrast-enhanced computed tomography of the chest showing mediastinal adenopathy led to a presumptive diagnosis of inhalational anthrax in both cases. The diagnoses were confirmed by blood cultures and polymerase chain reaction testing. Treatment with antibiotics, including intravenous ciprofloxacin, rifampin, and clindamycin, and supportive therapy appears to have slowed the progression of inhalational anthrax and has resulted to date in survival. [ABSTRACT FROM AUTHOR]

Objective: : The SARS-CoV-2 pandemic has shed light on the difficulties in spreading uniform information. We rely on national and international organizations to provide scientifically accurate information to the public at large. With so many different sources of information, often not scientific, there appears to be an incomplete understanding of many aspects of SARS-CoV-2 infection. We sought to gain information about healthcare worker understanding of the implications of a positive serum COVID-19 antibody test result. We identified a broad range of responses among all categories of healthcare workers in our facility. Most notably we found that there was not complete understanding that there can be asymptomatic spread of COVID-19 infection., Methods: : We provided health literacy and opinion questions to the healthcare workers of our facility., Results: : Upon analysis of the data, we identified many differences in level of understanding among our healthcare workers., Conclusion: : We identified a lack of consensus on important details leading to potentially growing uncertainty with respect to SARS-COV-2 antibody. A diminished health literacy with respect to antibody testing could potentially suggest future issues with understanding the importance of vaccination benefits., (© 2022 Fellowship of Postgraduate Medicine. Published by Elsevier Ltd. All rights reserved.)

In 2019, a novel coronavirus was identified in Wuhan, China. This strain was classified as a pandemic in early 2020 by the World Health Organization (WHO), rapidly reaching millions of cases worldwide and overwhelming intensive care units. One distinct feature identified in severe SARS-CoV-2 is abnormal and complex coagulation and hematologic abnormalities, including significantly elevated D-dimer and fibrin/fibrinogen values possibly increasing morbidity and mortality in this patient population. Aggressive anticoagulation therapy with appropriate peak anti-Xa level monitoring has produce satisfactory results at our institution. Our intent is to present a case series of our strategy to highlight the benefits of this approach., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Objective: Patients were observed to have variable temperatures. The objective of this study was to identify whether hypothermia in a patient infected with SARS-CoV-2 was associated with a higher than expected mortality., Methods: In total, 331 charts from patients hospitalized with SARS-CoV-2 between March 9 and April 20, 2020 were reviewed., Results: The probability of death was 2.06 times higher for those with hypothermia than for those without (95% CI 1.25-3.38)]. In ventilated patients, there were 32 deaths. Of these, 75% had been hypothermic. In a prior review of 10 000 non-SARS-CoV-2 patients with sepsis, the mortality rate in patients with hypothermia was 47%. A review of previous studies demonstrated a range of expected mortality rates in patients with ventilator-dependent respiratory failure and sepsis. In comparison, our study showed that within a group of critically ill patients with SARS-CoV-2 and hypothermia, the mortality rate exceeded those rates., Conclusion: Our review showed a significant association between hypothermia and death (p = 0.0033). Predictors of mortality in SARS-CoV-2 disease can expedite earlier aggressive care. Additionally, in areas with limited resources or overburdened healthcare systems, where there may be a need for resource allocation management, information about mortality risk may be helpful., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Ivermectin was shown to inhibit severe acute respiratory syndrome coronavirus 2 replication in vitro, which has led to off-label use, but clinical efficacy has not been described previously., Research Question: Does ivermectin benefit hospitalized coronavirus disease 2019 (COVID-19) patients?, Study Design and Methods: Charts of consecutive patients hospitalized at four Broward Health hospitals in Florida with confirmed COVID-19 between March 15 and May 11, 2020, treated with or without ivermectin were reviewed. Hospital ivermectin dosing guidelines were provided, but treatment decisions were at the treating physician's discretion. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included mortality in patients with severe pulmonary involvement, extubation rates for mechanically ventilated patients, and length of stay. Severe pulmonary involvement was defined as need for Fio 2  ≥ 50%, noninvasive ventilation, or invasive ventilation at study entry. Logistic regression and propensity score matching were used to adjust for confounders., Results: Two hundred eighty patients, 173 treated with ivermectin and 107 without ivermectin, were reviewed. Most patients in both groups also received hydroxychloroquine, azithromycin, or both. Univariate analysis showed lower mortality in the ivermectin group (15.0% vs 25.2%; OR, 0.52; 95% CI, 0.29-0.96; P = .03). Mortality also was lower among ivermectin-treated patients with severe pulmonary involvement (38.8% vs 80.7%; OR, 0.15; 95% CI, 0.05-0.47; P = .001). No significant differences were found in extubation rates (36.1% vs 15.4%; OR, 3.11; 95% CI, 0.88-11.00; P = .07) or length of stay. After multivariate adjustment for confounders and mortality risks, the mortality difference remained significant (OR, 0.27; 95% CI, 0.09-0.80; P = .03). One hundred ninety-six patients were included in the propensity-matched cohort. Mortality was significantly lower in the ivermectin group (13.3% vs 24.5%; OR, 0.47; 95% CI, 0.22-0.99; P < .05), an 11.2% (95% CI, 0.38%-22.1%) absolute risk reduction, with a number needed to treat of 8.9 (95% CI, 4.5-263)., Interpretation: Ivermectin treatment was associated with lower mortality during treatment of COVID-19, especially in patients with severe pulmonary involvement. Randomized controlled trials are needed to confirm these findings., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Myriad infectious and noninfectious causes of encephalomyelitis (EM) have similar clinical manifestations, presenting serious challenges to diagnosis and treatment. Metabolomics of cerebrospinal fluid (CSF) was explored as a method of differentiating among neurological diseases causing EM using a single CSF sample., Methodology/principal Findings: 1H NMR metabolomics was applied to CSF samples from 27 patients with a laboratory-confirmed disease, including Lyme disease or West Nile Virus meningoencephalitis, multiple sclerosis, rabies, or Histoplasma meningitis, and 25 controls. Cluster analyses distinguished samples by infection status and moderately by pathogen, with shared and differentiating metabolite patterns observed among diseases. CART analysis predicted infection status with 100% sensitivity and 93% specificity., Conclusions/significance: These preliminary results suggest the potential utility of CSF metabolomics as a rapid screening test to enhance diagnostic accuracies and improve patient outcomes., Competing Interests: The authors have declared that no competing interests exist

In traumatic optic neuropathy (TON), apoptosis of retinal ganglion cells is closely related to the local production of reactive oxygen species and inflammatory mediators from activated microglial cells. Adenosine receptor A2A (A2AAR) has been shown to possess anti-inflammatory properties that have not been studied in TON. In the present study, we examined the role of A2AAR in retinal complications associated with TON. Initial studies in wild-type mice revealed that treatment with the A2AAR agonist resulted in marked decreases in the TON-induced microglial activation, retinal cell death and releases of reactive oxygen species and pro-inflammatory cytokines TNF-α and IL-6. To further assess the role of A2AAR in TON, we studied the effects of A2AAR ablation on the TON-induced retinal abnormalities. A2AAR-/- mice with TON showed a significantly higher mRNA level of TNF-α, Iba1-1 in retinal tissue, and ICAM-1 expression in retinal sections compared with wild-type mice with TON. To explore a potential mechanism by which A2AAR-signaling regulates inflammation in TON, we performed additional studies using hypoxia- or LPS-treated microglial cells as an in vitro model for TON. Activation of A2AAR attenuates hypoxia or LPS-induced TNF-α release and significantly repressed the inflammatory signaling, ERK in the activated microglia. Collectively, this work provides pharmacological and genetic evidence for A2AAR signaling as a control point of cell death in TON and suggests that the retinal protective effect of A2AAR is mediated by attenuating the inflammatory response that occurs in microglia via interaction with MAPKinase pathway., (© 2013.)

Background: In a neonatal model of hypoxic pulmonary hypertension, a dramatic pulmonary artery adventitial thickening, accumulation of inflammatory cells in the adventitial compartment, and angiogenic expansion of the vasa vasorum microcirculatory network are observed. These pathophysiological responses suggest that rapidly proliferating vasa vasorum endothelial cells (VVEC) may exhibit increased permeability for circulating blood cells and macromolecules. However, the molecular mechanisms underlying these observations remain unexplored. Some reports implicated extracellular adenosine in the regulation of vascular permeability under hypoxic and inflammatory conditions. Thus, we aimed to determine the role of adenosine in barrier regulation of VVEC isolated from the pulmonary arteries of normoxic (VVEC-Co) or chronically hypoxic (VVEC-Hyp) neonatal calves., Principal Findings: We demonstrate via a transendothelial electrical resistance measurement that exogenous adenosine significantly enhanced the barrier function in VVEC-Co and, to a lesser extent, in VVEC-Hyp. Our data from a quantitative reverse transcription polymerase chain reaction show that both VVEC-Co and VVEC-Hyp express all four adenosine receptors (A1, A2A, A2B, and A3), with the highest expression level of A1 receptors (A1Rs). However, A1R expression was significantly lower in VVEC-Hyp compared to VVEC-Co. By using an A1R-specific agonist/antagonist and siRNA, we demonstrate that A1Rs are mostly responsible for adenosine-induced enhancement in barrier function. Adenosine-induced barrier integrity enhancement was attenuated by pretreatment of VVEC with pertussis toxin and GSK690693 or LY294002, suggesting the involvement of Gi proteins and the PI3K-Akt pathway. Moreover, we reveal a critical role of actin cytoskeleton in VVEC barrier regulation by using specific inhibitors of actin and microtubule polymerization. Further, we show that adenosine pretreatment blocked the tumor necrosis factor alpha (TNF-α)-induced permeability in VVEC-Co, validating its anti-inflammatory effects., Conclusions: We demonstrate for the first time that stimulation of A1Rs enhances the barrier function in VVEC by activation of the Gi/PI3K/Akt pathway and remodeling of actin microfilament.

Rabies is a rapidly progressive lyssavirus encephalitis that is statistically 100% fatal. There are no clinically effective antiviral drugs for rabies. An immunologically naïve teenager survived rabies in 2004 through improvised supportive care; since then, 5 additional survivors have been associated with use of the so-called Milwaukee Protocol (MP). The MP applies critical care focused on the altered metabolic and physiologic states associated with rabies. The aim of this study was to examine the metabolic profile of cerebrospinal fluid (CSF) from rabies patients during clinical progression of rabies encephalitis in survivors and nonsurvivors and to compare these samples with control CSF samples. Unsupervised clustering algorithms distinguished three stages of rabies disease and identified several metabolites that differentiated rabies survivors from those who subsequently died, in particular, metabolites related to energy metabolism and cell volume control. Moreover, for those patients who survived, the trajectory of their metabolic profile tracked toward the control profile and away from the rabies profile. NMR metabolomics of human rabies CSF provide new insights into the mechanisms of rabies pathogenesis, which may guide future therapy of this disease.

In diabetic retinopathy (DR), abnormalities in vascular and neuronal function are closely related to the local production of inflammatory mediators whose potential source is microglia. Adenosine and its receptors have been shown to possess anti-inflammatory properties that have only recently been studied in DR. Here, we review recent studies that determined the roles of adenosine and its associated proteins, including equilibrative nucleoside transporters, adenosine receptors, and underlying signaling pathways in retinal complications associated with diabetes.

Purpose: Degenerative retinal diseases are characterized by inflammation and microglial activation. The nonpsychoactive cannabinoid, cannabidiol (CBD), is an anti-inflammatory in models of diabetes and glaucoma. However, the cellular and molecular mechanisms are largely unknown. We tested the hypothesis that retinal inflammation and microglia activation are initiated and sustained by oxidative stress and p38 mitogen-activated protein kinase (MAPK) activation, and that CBD reduces inflammation by blocking these processes., Methods: Microglial cells were isolated from retinas of newborn rats. Tumor necrosis factor (TNF)-alpha levels were estimated with ELISA. Nitric oxide (NO) was determined with a NO analyzer. Superoxide anion levels were determined by the chemiluminescence of luminol derivative. Reactive oxygen species (ROS) was estimated by measuring the cellular oxidation products of 2', 7'-dichlorofluorescin diacetate., Results: In retinal microglial cells, treatment with lipopolysaccharide (LPS) induced immediate NADPH oxidase-generated ROS. This was followed by p38 MAPK activation and resulted in a time-dependent increase in TNF-alpha production. At a later phase, LPS induced NO, ROS, and p38 MAPK activation that peaked at 2-6 h and was accompanied by morphological change of microglia. Treatment with 1 microM CBD inhibited ROS formation and p38 MAPK activation, NO and TNF-alpha formation, and maintained cell morphology. In addition, LPS-treated rat retinas showed an accumulation of macrophages and activated microglia, significant levels of ROS and nitrotyrosine, activation of p38 MAPK, and neuronal apoptosis. These effects were blocked by treatment with 5 mg/kg CBD., Conclusions: Retinal inflammation and degeneration in uveitis are caused by oxidative stress. CBD exerts anti-inflammatory and neuroprotective effects by a mechanism that involves blocking oxidative stress and activation of p38 MAPK and microglia.

The radiographic and computed tomographic (CT) findings in two patients with documented inhalational anthrax resulting from bioterrorism exposure are presented. Chest radiographs demonstrated mediastinal widening, adenopathy, pleural effusions, and air-space disease. Chest CT images revealed enlarged hyperattenuating mediastinal and hilar lymph nodes and edema of mediastinal fat. Chest CT findings are helpful for making the initial diagnosis. To the authors' knowledge, the spectrum and follow-up of CT findings have not been previously described.