48-year-old with Coronavirus Disease 2019

Case Presentation: A 48-year-old male who presented with signs and symptoms suggestive of an upper respiratory infection was seen at an urgent care, he had a negative chest radiograph and was discharged. With no other cases of coronavirus disease 2019 (COVID-19) in the state, the patient presented to the emergency department two days later with worsening shortness of breath.Discussion: There are a variety of findings on both chest radiograph and computed tomography of the chest that suggests COVID-19

Newer Surveillance Data Extends Our Understanding of the Niche of \u3ci\u3eRickettsia montanensis\u3c/i\u3e (Rickettsiales: Rickettsiaceae) Infection of the American Dog Tick (Acari: Ixodidae) in the United States

Background: Understanding the geographic distribution of Rickettsia montanensis infections in Dermacentor variabilis is important for tick-borne disease management in the United States, as both a tick-borne agent of interest and a potential confounder in surveillance of other rickettsial diseases. Two previous studies modeled niche suitability for D. variabilis with and without R. montanensis, from 2002-2012, indicating that the D. variabilis niche overestimates the infected niche. This study updates these, adding data since 2012. Methods: Newer surveillance and testing data were used to update Species Distribution Models (SDMs) of D. variabilis, and R. montanensis infected D. variabilis, in the United States. Using random forest (RF) models, found to perform best in previous work, we updated the SDMs and compared them with prior results. Warren’s I niche overlap metric was used to compare between predicted suitability for all ticks and ‘pathogen positive niche’ models across datasets. Results: Warren’s I indicated \u3c 2% change in predicted niche, and there was no change in order of importance of environmental predictors, for D. variabilis or R. montanensis positive niche. The updated D. variabilis niche model overpredicted suitability compared to the updated R. montanensis positive niche in key peripheral parts of the range, but slightly underpredicted through the northern and midwestern parts of the range. This reinforces previous findings of a more constrained pathogen-positive niche than predicted by D. variabilis records alone. Conclusions: The consistency of predicted niche suitability for D. variabilis in the United States, with the addition of nearly a decade of new data, corroborates this is a species with generalist habitat requirements. Yet a slight shift in updated niche distribution, even of low suitability, included more southern areas, pointing to a need for continued and extended monitoring and surveillance. This further underscores the importance of revisiting vector and vector-borne disease distribution maps

Nox2 Inhibition Regulates Stress Response and Mitigates Skeletal Muscle Fiber Atrophy during Simulated Microgravity

Insufficient stress response and elevated oxidative stress can contribute to skeletal muscle atrophy during mechanical unloading (e.g., spaceflight and bedrest). Perturbations in heat shock proteins (e.g., HSP70), antioxidant enzymes, and sarcolemmal neuronal nitric oxidase synthase (nNOS) have been linked to unloading-induced atrophy. We recently discovered that the sarcolemmal NADPH oxidase-2 complex (Nox2) is elevated during unloading, downstream of angiotensin II receptor 1, and concomitant with atrophy. Here, we hypothesized that peptidyl inhibition of Nox2 would attenuate disruption of HSP70, MnSOD, and sarcolemmal nNOS during unloading, and thus muscle fiber atrophy. F344 rats were divided into control (CON), hindlimb unloaded (HU), and hindlimb unloaded +7.5 mg/kg/day gp91ds-tat (HUG) groups. Unloading-induced elevation of the Nox2 subunit p67phox-positive staining was mitigated by gp91ds-tat. HSP70 protein abundance was significantly lower in HU muscles, but not HUG. MnSOD decreased with unloading; however, MnSOD was not rescued by gp91ds-tat. In contrast, Nox2 inhibition protected against unloading suppression of the antioxidant transcription factor Nrf2. nNOS bioactivity was reduced by HU, an effect abrogated by Nox2 inhibition. Unloading-induced soleus fiber atrophy was significantly attenuated by gp91ds-tat. These data establish a causal role for Nox2 in unloading-induced muscle atrophy, linked to preservation of HSP70, Nrf2, and sarcolemmal nNOS

Spatio-temporal patterns and characteristics of swine shipments in the U.S. based on Interstate Certificates of Veterinary Inspection

Domestic swine production in the United States is a critical economic and food security industry, yet there is currently no large-scale quantitative assessment of swine shipments available to support risk assessments. In this study, we provide a national-level characterization of the swine industry by quantifying the demographic (i.e. age, sex) patterns, spatio-temporal patterns, and the production diversity within swine shipments. We characterize annual networks of swine shipments using a 30% stratified sample of Interstate Certificates of Veterinary Inspection (ICVI), which are required for the interstate movement of agricultural animals. We used ICVIs in 2010 and 2011 from eight states that represent 36% of swine operations and 63% of the U.S. swine industry. Our analyses reflect an integrated and spatially structured industry with high levels of spatial heterogeneity. Most shipments carried young swine for feeding or breeding purposes and carried a median of 330 head (range: 1–6,500). Geographically, most shipments went to and were shipped from Iowa, Minnesota, and Nebraska. This work, therefore, suggests that although the swine industry is variable in terms of its size and type of swine, counties in states historically known for breeding and feeding operations are consistently more central to the shipment network

Spatio-temporal patterns and characteristics of swine shipments in the U.S. based on Interstate Certificates of Veterinary Inspection

Domestic swine production in the United States is a critical economic and food security industry, yet there is currently no large-scale quantitative assessment of swine shipments available to support risk assessments. In this study, we provide a national-level characterization of the swine industry by quantifying the demographic (i.e. age, sex) patterns, spatio-temporal patterns, and the production diversity within swine shipments. We characterize annual networks of swine shipments using a 30% stratified sample of Interstate Certificates of Veterinary Inspection (ICVI), which are required for the interstate movement of agricultural animals. We used ICVIs in 2010 and 2011 from eight states that represent 36% of swine operations and 63% of the U.S. swine industry. Our analyses reflect an integrated and spatially structured industry with high levels of spatial heterogeneity. Most shipments carried young swine for feeding or breeding purposes and carried a median of 330 head (range: 1–6,500). Geographically, most shipments went to and were shipped from Iowa, Minnesota, and Nebraska. This work, therefore, suggests that although the swine industry is variable in terms of its size and type of swine, counties in states historically known for breeding and feeding operations are consistently more central to the shipment network

Rapid Exchange Cooling with Trapped Ions

The trapped-ion quantum charge-coupled device (QCCD) architecture is a leading candidate for advanced quantum information processing. In current QCCD implementations, imperfect ion transport and anomalous heating can excite ion motion during a calculation. To counteract this, intermediate cooling is necessary to maintain high-fidelity gate performance. Cooling the computational ions sympathetically with ions of another species, a commonly employed strategy, creates a significant runtime bottleneck. Here, we demonstrate a different approach we call exchange cooling. Unlike sympathetic cooling, exchange cooling does not require trapping two different atomic species. The protocol introduces a bank of $"$coolant$"$ ions which are repeatedly laser cooled. A computational ion can then be cooled by transporting a coolant ion into its proximity. We test this concept experimentally with two ions, executing the necessary transport in 107 $\mu s$, an order of magnitude faster than typical sympathetic cooling durations. We remove over 96%, and as many as 102(5) quanta, of axial motional energy from the computational ion. We verify that re-cooling the coolant ion does not decohere the computational ion. This approach validates the feasibility of a single-species QCCD processor, capable of fast quantum simulation and computation

Quantitative Factors Proposed to Influence the Prevalence of Canine Tick-Bourne Disease Agents in the United States

The Companion Animal Parasite Council hosted a meeting to identify quantifiable factors that can influence the prevalence of tick-borne disease agents among dogs in North America. This report summarizes the approach used and the factors identified for further analysis with mathematical models of canine exposure to tick-borne pathogens

Halofuginone inhibits TGF-β/BMP signaling and in combination with zoledronic acid enhances inhibition of breast cancer bone metastasis

More efficient therapies that target multiple molecular mechanisms are needed for the treatment of incurable bone metastases. Halofuginone is a plant alkaloid-derivative with antiangiogenic and antiproliferative effects. Here we demonstrate that halofuginone is an effective therapy for the treatment of bone metastases, through multiple actions that include inhibition of TGFβ and BMP-signaling., Halofuginone blocked TGF-β-signaling in MDA-MB-231 and PC3 cells showed by inhibition of TGF-β–induced Smad-reporter, phosphorylation of Smad-proteins, and expression of TGF-β-regulated metastatic genes. Halofuginone increased inhibitory Smad7-mRNA and reduced TGF-β-receptor II protein. Proline supplementation but not Smad7-knockdown reversed halofuginone-inhibition of TGF-β-signaling. Halofuginone also decreased BMP-signaling. Treatment of MDA-MB-231 and PC3 cells with halofuginone reduced the BMP-Smad-reporter (BRE)4, Smad1/5/8-phosphorylation and mRNA of the BMP-regulated gene Id-1. Halofuginone decreased immunostaining of phospho-Smad2/3 and phospho-Smad1/5/8 in cancer cells in vivo., Furthermore, halofuginone decreased tumor-take and growth of orthotopic-tumors. Mice with breast or prostate bone metastases treated with halofuginone had significantly less osteolysis than control mice. Combined treatment with halofuginone and zoledronic-acid significantly reduced osteolytic area more than either treatment alone. Thus, halofuginone reduces breast and prostate cancer bone metastases in mice and combined with treatment currently approved by the FDA is an effective treatment for this devastating complication of breast and prostate-cancer

Tumor-expressed adrenomedullin accelerates breast cancer bone metastasis

INTRODUCTION: Adrenomedullin (AM) is secreted by breast cancer cells and increased by hypoxia. It is a multifunctional peptide that stimulates angiogenesis and proliferation. The peptide is also a potent paracrine stimulator of osteoblasts and bone formation, suggesting a role in skeletal metastases-a major site of treatment-refractory tumor growth in patients with advanced disease. METHODS: The role of adrenomedullin in bone metastases was tested by stable overexpression in MDA-MB-231 breast cancer cells, which cause osteolytic bone metastases in a standard animal model. Cells with fivefold increased expression of AM were characterized in vitro, inoculated into immunodeficient mice and compared for their ability to form bone metastases versus control subclones. Bone destruction was monitored by X-ray, and tumor burden and osteoclast numbers were determined by quantitative histomorphometry. The effects of AM overexpression on tumor growth and angiogenesis in the mammary fat pad were determined. The effects of AM peptide on osteoclast-like multinucleated cell formation were tested in vitro. A small-molecule AM antagonist was tested for its effects on AM-stimulated ex vivo bone cell cultures and co-cultures with tumor cells, where responses of tumor and bone were distinguished by species-specific real-time PCR. RESULTS: Overexpression of AM mRNA did not alter cell proliferation in vitro, expression of tumor-secreted factors or cell cycle progression. AM-overexpressing cells caused osteolytic bone metastases to develop more rapidly, which was accompanied by decreased survival. In the mammary fat pad, tumors grew more rapidly with unchanged blood vessel formation. Tumor growth in the bone was also more rapid, and osteoclasts were increased. AM peptide potently stimulated bone cultures ex vivo; responses that were blocked by small-molecule adrenomedullin antagonists in the absence of cellular toxicity. Antagonist treatment dramatically suppressed tumor growth in bone and decreased markers of osteoclast activity. CONCLUSIONS: The results identify AM as a target for therapeutic intervention against bone metastases. Adrenomedullin potentiates osteolytic responses in bone to metastatic breast cancer cells. Small-molecule antagonists can effectively block bone-mediated responses to tumor-secreted adrenomedullin, and such agents warrant development for testing in vivo