Alternative Approach to Sand Bags for Flood Prevention Through the use of 3D Printed Flood Panels

This is an alternative approach to sand bags which could save time and money when implementing temporary barriers around critical areas during times of flooding in flood plains or areas near rivers

Rhodium-Catalyzed Endo -Selective Epoxide-Opening Cascades: Formal Synthesis of (−)-Brevisin

[Rh(CO)₂Cl]₂ is as an effective catalyst for endo-selective cyclizations and cascades of epoxy-(E)-enoate alcohols, thus enabling the synthesis of oxepanes and oxepane-containing polyethers from di- and trisubstituted epoxides. Syntheses of the ABC and EF ring systems of (−)-brevisin via all endo-diepoxide-opening cascades using this method constitute a formal total synthesis and demonstrate the utility of this methodology in the context of the synthesis of marine ladder polyether natural products.National Institute of General Medical Sciences (U.S.) (GM72566)National Institute of General Medical Sciences (U.S.) (F32GM095014

CSF Inflammatory Markers Differ in Gram-Positive Versus Gram-negative Shunt Infections.

BACKGROUND: Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection. METHODS: We conducted a retrospective chart review of children with culture-confirmed CSF shunt infection at Children\u27s Hospital and Medical Center from July 2013 to December 2015. CSF cytokine analysis was performed for those patients with CSF in frozen storage from the same sample that was used for diagnostic culture. RESULTS: A total of 12 infections were included in this study. Patients with shunt infection had a median C-reactive protein (CRP) of 18.25 mg/dL. Median peripheral white blood cell count was 15.53 × 10 CONCLUSIONS: This pilot study is the first to characterize the CSF cytokine profile in patients with CSF shunt infection and supports the distinction of chemokine and cytokine profiles between gram-negative and gram-positive infections. Additionally, it demonstrates the potential of CSF chemokines and cytokines as biomarkers for the diagnosis of shunt infection

Stereoelectronic Model To Explain Highly Stereoselective Reactions of Seven-Membered-Ring Oxocarbenium-Ion Intermediates

Nucleophilic attack on seven-membered-ring oxocarbenium ions is generally highly stereoselective. The preferred mode of nucleophilic attack forms the product in a conformation that minimizes transannular interactions, thus leading to different stereoselectivity as compared to that of reactions involving six-membered-ring oxocarbenium ions

Differential Expression of Chemokines in a Mouse Model of Wound Healing

Macrophages have a multifaceted role in wound healing. While their initial activity may be in the degradation and elimination of damaged tissue, macrophages also produce and secrete a variety of mediators that can participate in the repair process as well. To perform these functions, macrophages must be recruited to a wound site. Our purpose was to examine the temporal and spatial expression of macrophage chemoattracting cytokines (chemokines) at a surgical wound site. A surgical wound was prepared on the dorsal aspect of B6AFI/J mice. Biopsies were obtained from the wound and a comparable nonwounded area between 6 and 72 hr after wounding. The presence or absence of various chemokine mRNAs was detected by the reverse transcriptase-polymerase chain reaction (RT-PCR). Immunohistochemical staining and in situ RT-PCR determined localization of cells producing chemokines. In wounded tissue, both macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP -1) were detected; however, the time of expression differed for each molecule. MCP-1 mRNA was detected at 6 hr after wounding, with decreased expression at subsequent time periods. In contrast, MIP-1 messages were not observed until 24 hr after wounding, and steadily increased thereafter. MCP-1 and MIP-1 mRNA and protein were localized predominantly in keratinocytes. The rapid and strong expression of MCP-1 and MIP -1 messages within the wound site suggests a pivotal role for these chemokines in the repair process. The differences in appearance and level of expression over time, however, suggest distinctive functions for each chemokine and indicate that the local milieu, rather than a single cytokine, influences macrophage recruitment and/or activation

IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection.

BACKGROUND: Shunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus. Previous studies have shown an attenuated immune response to these biofilm-mediated infections. We proposed that IL-10 reduces the inflammatory response to Staphylococcus epidermidis (S. epidermidis) CNS catheter infection. METHODS: In this study, a murine model of catheter-associated S. epidermidis biofilm infection in the CNS was generated based on a well-established similar model for S. aureus. The catheters were pre-coated with a clinically derived biofilm-forming strain of S. epidermidis (strain 1457) which were then stereotactically implanted into the lateral left ventricle of 8-week-old C57BL/6 and IL-10 knockout (IL-10 knockout) mice. Bacterial titers as well as cytokine and chemokine levels were measured at days 3, 5, 7, and 10 in mice implanted with sterile and S. epidermidis-coated catheters. RESULTS: Cultures demonstrated a catheter-associated and parenchymal infection that persisted through 10 days following infection. Cytokine analysis of the tissue surrounding the catheters revealed greater levels of IL-10, an anti-inflammatory cytokine, in the infected group compared to the sterile. In IL-10 KO mice, we noted no change in bacterial burdens, showing that IL-10 is not needed to control the infection in a CNS catheter infection model. However, IL-10 KO mice had increased levels of pro-inflammatory mediators in the tissues immediately adjacent to the infected catheter, as well as an increase in weight loss. CONCLUSIONS: Together our results indicate that IL-10 plays a key role in regulating the inflammatory response to CNS catheter infection but not in control of bacterial burdens. Therefore, IL-10 may be a useful therapeutic target for immune modulation in CNS catheter infection but this should be used in conjunction with antibiotic therapy for bacterial eradication

Staphylococcus aureus sarA regulates inflammation and colonization during central nervous system biofilm formation

Infection is a frequent and serious complication following the treatment of hydrocephalus with CSF shunts, with limited therapeutic options because of biofilm formation along the catheter surface. Here we evaluated the possibility that the sarA regulatory locus engenders S. aureus more resistant to immune recognition in the central nervous system (CNS) based on its reported ability to regulate biofilm formation. We utilized our established model of CNS catheter-associated infection, similar to CSF shunt infections seen in humans, to compare the kinetics of bacterial titers, cytokine production and inflammatory cell influx elicited by wild type S. aureus versus an isogenic sarA mutant. The sarA mutant was more rapidly cleared from infected catheters compared to its isogenic wild type strain. Consistent with this finding, several pro-inflammatory cytokines and chemokines, including IL-17, CXCL1, and IL-1β were significantly increased in the brain following infection with the sarA mutant versus wild type S. aureus, in agreement with the fact that the sarA mutant displayed impaired biofilm growth and favored a planktonic state. Neutrophil influx into the infected hemisphere was also increased in the animals infected with the sarA mutant compared to wild type bacteria. These changes were not attributable to extracellular protease activity, which is increased in the context of SarA mutation, since similar responses were observed between sarA and a sarA/protease mutant. Overall, these results demonstrate that sarA plays an important role in attenuating the inflammatory response during staphylococcal biofilm infection in the CNS via a mechanism that remains to be determined

Bacteria Commonly Associated with Central Nervous System Catheter Infections Elicit Distinct CSF Proteome Signatures

Background: Cerebrospinal fluid (CSF) shunt infection is a common and devastating complication of the treatment of hydrocephalus. Timely and accurate diagnosis is essential as these infections can lead to long-term neurologic consequences including seizures, decreased intelligence quotient (IQ) and impaired school performance in children. Currently the diagnosis of shunt infection relies on bacterial culture; however, culture is not always accurate since these infections are frequently caused by bacteria capable of forming biofilms, such as Staphylococcus epidermidis, Cutibacterium acnes, and Pseudomonas aeruginosa resulting in few planktonic bacteria detectable in the CSF. Therefore, there is a critical need to identify a new rapid, and accurate method for diagnosis of CSF shunt infection with broad bacterial species coverage to improve the long-term outcomes of children suffering from these infections. Methods: To investigate potential biomarkers that would discriminate S. epidermidis, C. acnes and P. aeruginosa central nervous system (CNS) catheter infection we leveraged our previously published rat model of CNS catheter infection to perform serial CSF sampling to characterize the CSF proteome during these infections compared to sterile catheter placement. Results: P. aeruginosa infection demonstrated a far greater number of differentially expressed proteins when compared to S. epidermidis and C. acnes infection and sterile catheters, and these changes persisted throughout the 56-day time course. S. epidermidis demonstrated an intermediate number of differentially expressed proteins, primarily at early time points that dissipated over the course of infection. C. acnes induced the least amount of change in the CSF proteome when compared to the other pathogens. Conclusions: Despite the differences in the CSF proteome with each organism compared to sterile injury, several proteins were common across all bacterial species, especially at day 5 post-infection, which are candidate diagnostic biomarkers

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

Multidisciplinary engagement for fencing research informs efficacy and rancher-to-researcher knowledge exchange

Across much of the Western United States, recovery of large carnivore populations is creating new challenges for livestock producers. Reducing the risks of sharing the landscape with recovering wildlife populations is critical to private working lands, which play an vital role in securing future energy, water, food, and fiber for an ever-expanding human population. Fencing is an important mitigation practice that many ranchers, land managers, and conservationists implement to reduce carnivore-livestock conflict. While fencing strategies have been reviewed in the literature, research seldom incorporates knowledge from the people who utilize fencing the most (i.e., livestock producers). Incorporating producers and practitioners early in the process of producing scientific knowledge is proving to be a critical endeavor for enhancing knowledge exchange, better evaluation of the practice, and more realistic understanding of the costs and benefits. Here, we describe how our multidisciplinary effort of co-producing knowledge informs understanding of the effectiveness of various fencing designs and more importantly provides a better mechanism for transferring this knowledge between producers, researchers, and land managers. We explain the process underway and demonstrate that incorporating producers and practitioners from the onset allows research priorities and expected outcomes to be set collaboratively, gives transparency to the agricultural community of the research process, provides a critical lens to evaluate efficacy and functionality, and will inform the practicality of fencing as a conflict prevention tool. We discuss opportunities and challenges of this co-production process and how it can be applied to other realms of fencing and conflict prevention strategies