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Objective:To review the microbiological activity, safety, and efficacy of the new fluoroquinolone delafloxacin for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Data Sources:A PubMed search from 1945 to September 2018 was done using the terms delafloxacin, acute bacterial skin and skin structure infections, skin and soft tissue infections, and fluoroquinolone. Additional sources include the Food and Drug Administration website, ClinicalTrials.gov, and the Melinta Therapeutics website. Study Selection and Data Extraction:The literature search was limited to those published in the English language and included in vitro and human studies that evaluated microbiological coverage, pharmacokinetics, pharmacodynamics, safety, and/or efficacy. Data Synthesis:Delafloxacin is a new fluoroquinolone with a unique structure for its class that covers both methicillin-resistant Staphylococcus aureus(MRSA) and Pseudomonas. This new antibiotic has demonstrated noninferiority to vancomycin plus aztreonam for the treatment of ABSSSIs in both an intravenous-only regimen and an intravenous to an oral regimen. Relevance to Patient Care and Clinical Practice:ABSSSIs are infections that are most often caused by Staphylococcusand represent one of the most common types of hospital infections. MRSA represents about half of all staphylococcal skin infections, and along with gram-negative infections, increase the rates of patient morbidity and health care costs. Delafloxacin is an additional treatment option that covers both of these types of microorganisms. Conclusions:Delafloxacin is a safe and effective treatment option for ABSSSIs, particularly in those with polymicrobial infections and those with MRSA.

In this experiment, blast furnace slag fine aggregate that was produced by 3 different steel factory was been used in high-strength concrete, and mechanical properties of high-strength concrete were studied. The concrete using the blast furnace slag fine aggregate is admitted the increase of compressive strength as well as the case of the river sand when the water cement ratio is reduced, and the compressive strength can attain 100N/mm2. The strength of concrete using blast furnace slag fine aggregate is lower than the strength of concrete using natural river sand as fine aggregate, and the strength of concrete using mixture fine aggregate is middle of strength used river sand and strength used blast furnace slag fine aggregate. The crushing value of blast furnace slag fine aggregate is bigger than the natural river sand, and it could influence the strength of high-strength concrete using blast furnace slag fine aggregate.

The development of effective therapeutic vaccines to generate tumor-reactive cytotoxic T lymphocytes (CTLs) continues to be a top research priority. However, in spite of some promising results, there are no clear examples of vaccines that eradicate established tumors. Most vaccines are ineffective because they generate low numbers of CTLs and because numerous immunosuppressive factors abound in tumor-bearing hosts. We designed a peptide vaccine that produces large numbers of tumor-reactive CTLs in a mouse model of melanoma. Surprisingly, CTL tumor recognition and antitumor effects decreased in the presence of interferon γ (IFNγ), a cytokine that can provide therapeutic benefit. Tumors exposed to IFNγ evade CTLs by inducing large amounts of noncognate major histocompatibility complex class I molecules, which limit T-cell activation and effector function. Our results demonstrate that peptide vaccines can eradicate large, established tumors in circumstances under which the inhibitory activities of IFNγ are curtailed.

The development of effective therapeutic vaccines to generate tumor-reactive cytotoxic T lymphocytes (CTLs) continues to be a top research priority. However, in spite of some promising results, there are no clear examples of vaccines that eradicate established tumors. Most vaccines are ineffective because they generate low numbers of CTLs and because numerous immunosuppressive factors abound in tumor-bearing hosts. We designed a peptide vaccine that produces large numbers of tumor-reactive CTLs in a mouse model of melanoma. Surprisingly, CTL tumor recognition and antitumor effects decreased in the presence of interferon γ (IFNγ), a cytokine that can provide therapeutic benefit. Tumors exposed to IFNγ evade CTLs by inducing large amounts of noncognate major histocompatibility complex class I molecules, which limit T-cell activation and effector function. Our results demonstrate that peptide vaccines can eradicate large, established tumors in circumstances under which the inhibitory activities of IFNγ are curtailed.

The main targets for the immunosuppressive calcineurin inhibitors, cyclosporin A (CsA) and tacrolimus, have been considered to be activated T cells, but not antigen-presenting cells. Here we demonstrate that CsA and tacrolimus, but not rapamycin, inhibit major histocompatibility complex (MHC)–restricted antigen presentation in dendritic cells (DCs). Microencapsulated ovalbumin (OVA) was efficiently captured, processed, and presented on both class I MHC molecules (cross-presentation) as well as on class II MHC molecules. Addition of CsA and tacrolimus, but not rapamycin, to cultures of DCs inhibited both the class I processing pathway and the class II processing pathway of exogenous OVA. In addition, CsA and tacrolimus, but not rapamycin, also inhibited the classic class I processing pathway of endogenous OVA. CsA and tacrolimus did not inhibit presentation of exogenously added OVA peptide, SIINFEKL, phagocytic activity of DCs, or the total level of expression of class I MHC (H-2Kb) molecules. CsA and tacrolimus, however, inhibited profoundly the expression of SIINFEKL-H-2Kb complexes in OVA-phagocytized DCs. These results demonstrate clearly that CsA and tacrolimus inhibit intracellular processing events of antigens, and further suggest that the immunosuppressive activity of CsA and tacrolimus is at least in part due to inhibition of antigen processing pathways.

The main targets for the immunosuppressive calcineurin inhibitors, cyclosporin A (CsA) and tacrolimus, have been considered to be activated T cells, but not antigen-presenting cells. Here we demonstrate that CsA and tacrolimus, but not rapamycin, inhibit major histocompatibility complex (MHC)–restricted antigen presentation in dendritic cells (DCs). Microencapsulated ovalbumin (OVA) was efficiently captured, processed, and presented on both class I MHC molecules (cross-presentation) as well as on class II MHC molecules. Addition of CsA and tacrolimus, but not rapamycin, to cultures of DCs inhibited both the class I processing pathway and the class II processing pathway of exogenous OVA. In addition, CsA and tacrolimus, but not rapamycin, also inhibited the classic class I processing pathway of endogenous OVA. CsA and tacrolimus did not inhibit presentation of exogenously added OVA peptide, SIINFEKL, phagocytic activity of DCs, or the total level of expression of class I MHC (H-2Kb) molecules. CsA and tacrolimus, however, inhibited profoundly the expression of SIINFEKL-H-2Kbcomplexes in OVA-phagocytized DCs. These results demonstrate clearly that CsA and tacrolimus inhibit intracellular processing events of antigens, and further suggest that the immunosuppressive activity of CsA and tacrolimus is at least in part due to inhibition of antigen processing pathways.

Increased use of digital imagery has facilitated the opportunity to use features, in addition to points, in photogrammetric applications. Straight lines are often present in object space, and prior research has focused on incorporating straight–line constraints into bundle adjustment for frame imagery. In the research reported in this paper, object–space straight lines are used in a bundle adjustment with self–calibration. The perspective projection of straight lines in the object space produces straight lines in the image space in the absence of distortions. Any deviations from straightness in the image space are attributed to various distortion sources, such as radial and decentric lens distortions. Before incorporating straight lines into a bundle adjustment with self–calibration, the representation and perspective transformation of straight lines between image space and object space should be addressed. In this investigation, images of straight lines are represented as a sequence of points along the image line. Also, two points along the object–space straight line are used to represent that line. The perspective relationship between image– and object–space lines is incorporated in a mathematical constraint. The underlying principle in this constraint is that the vector from the perspective centre to an image point on a straight–line feature lies on the plane defined by the perspective centre and the two object points defining the straight line. This constraint has been embedded in a software application for bundle adjustment with self–calibration that can incorporate point as well as straight–line features. Experiments with simulated and real data have proved the feasibility and the efficiency of the algorithm proposed.

We previously reported that hepatocyte growth factor (HGF) had a stimulatory effect on hair growth in vivo and in vitro. The secreted inactive form of HGF is processed into an active form by serine proteinases such as HGF activator and urokinase. The mRNA expressions of various proteinases and their inhibitors in relation to HGF activation in hair growth were examined using animals with a synchronous hair cycle. Total RNA were extracted from the anterior dorsal skin of rats in different hair cycle stages, and mRNA expressions of the specific genes were compared using semiquantitative reverse transcription polymerase chain reaction. The mRNA of HGF, HGF activator, urokinase, plasminogen activator inhibitor (PAI)-1, nexin-1, matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase (TIMP)-1 were expressed strongly in anagen tissue and slightly in telogen tissue. Moreover, topical application of 1% minoxidil sulfate to the anterior dorsal skin of rats in telogen stimulated hair growth and increased the mRNA expressions of HGF and MMP-2. These findings suggest that some proteinases and their inhibitors, strongly expressed in anagen, may act as hair growth regulatory molecules, and may also be involved in processing the latent form of HGF.Journal of Investigative Dermatology Symposium Proceedings (2004) 4, 312–315; doi:10.1038/sj.jidsp.5640236

Background: Sepsis and septic shock are severe medical conditions that can damage multiple organs with a higher risk of mortality. Recently, the combination of hydrocortisone, ascorbic acid and thiamine (HAT) was hypothesized to work synergistically to reverse septic shock and reduce mortality.Aim: To ascertain the efficacy of HAT therapy and compare whether HAT therapy is more beneficial compared to the standard of care in sepsis and septic shock patients.Methods: PubMed, Clinicaltrials.gov, Scopus, Web of Science, Cochrane and Embase are databases that were used to identify trials that conducted a study of the combination of HAT in sepsis or septic shock.Results: There were 134 articles identified through a database search and 16 from other sources, which were subsequently reduced to 11 trials (six randomized trials and five non-randomized trials) that were deemed appropriate for inclusion in this review. Most of the outcomes from these studies focused on mortality, the need for renal replacement therapy, duration of vasopressor use, changes in Sequential Organ Failure Assessment score, procalcitonin clearance and lengths of intensive care unit stay.Conclusion: Due to inconsistent results from clinical studies, the benefits of HAT therapy cannot be confirmed at this point in sepsis and septic shock. Currently, there are at least 20 randomized controlled trials testing HAT in various combinations and dosages in patients with severe sepsis and septic shock. The results of these studies are required before definitive conclusions can be made regarding the impact of this novel treatment strategy on the morbidity and mortality of patients with sepsis.