Echinocandins are a first-line therapy for candidemia and invasive candidiasis. They are generally safe with few drug interactions, but the stability and pharmacokinetic properties of currently approved echinocandins are such that each was developed for daily intravenous infusion. We sought to discover a novel echinocandin with properties that would enable more flexible dosing regimens, alternate routes of delivery, and expanded utility. Derivatives of known echinocandin scaffolds were generated, and an iterative process of design and screening led to the discovery of CD101, a novel echinocandin that has since demonstrated improved chemical stability and pharmacokinetics. Here, we report the structure-activity relationships (including preclinical efficacy and pharmacokinetic data) for the series of echinocandin analogs from which CD101 was selected. In a mouse model of disseminated candidiasis, the test compounds displayed clear dose responses and were generally associated with lower fungal burdens than that of anidulafungin. Single-dose pharmacokinetic studies in beagle dogs revealed a wide disparity in the half-lives and volumes of distribution, with one compound (now known as CD101) displaying a half-life that is nearly 5-fold longer than that of anidulafungin (53.1 h versus 11.6 h, respectively). In vitro activity data against panels of Candida spp. and Aspergillus spp. demonstrated that CD101 behaved similarly to approved echinocandins in terms of potency and spectrum of activity, suggesting that the improved efficacy observed in vivo for CD101 is a result of features beyond the antifungal potency inherent to the molecule. Factors that potentially contribute to the improved in vivo efficacy of CD101 are discussed.

Congestive heart failure (CHF) is a complex syndrome involving altered neurohormonal levels and impaired cardiac and renal function. In recent years, intravenous administration of exogenous human brain-type natriuretic peptide (hBNP) has become an important therapy in treating patients with acutely decompensated CHF. However, reports during the past year suggest that hBNP could play a prominent role in the chronic treatment of CHF patients as well. We are currently developing conjugates of hBNP suitable for oral delivery to provide a patient-friendly treatment option for chronic heart failure patients. In this report, we present in vitro activity results obtained from hBNP conjugates featuring a variety of rationally designed amphiphilic oligomers. Mapping studies revealed that the hydrophobic/hydrophilic balance of the oligomer impacted the regioselectivity of conjugation. Additionally, the regiochemistry and extent of conjugation had a significant impact on activity. Many monoconjugates retained activity comparable to native peptide and are currently under evaluation in subsequent in vivo screens.

Smart Textiles integrated with communicating components have been used in the military for many applications. The wearable antenna can be attached or embedded into smart textiles which could be used for communication between combat soldiers in the battlefield. This paper presents the design of three different polygon shaped patch antennas operating on 3G Mobile Band frequency 2100 MHz embedded on three different dielectric constant materials for Military applications. The proposed polygon shaped patch antenna introduces horizontal slit in its patch to improve the antenna performance. The slit length is varied and their corresponding effect on the antenna performance is analyzed.

No abstract

Objective: To evaluate the common causes of preanalytical errors in a fully automated hematology laboratory. Methods: Laboratory staff was instructed to record the rejected samples and the causes of such rejections of ward and outpatient samples collected in both wards and laboratory. Results: Of the 53344 samples received for hematological tests during the one year period from 1.1.2016 to 31.12.2016, 181 samples were rejected for analysis. This accounted for 0.3% of samples collected for hematological tests. The reasons for rejections with their incidences are as follows: Insufficient samples-35.3 %, Clotted sample-25.7 %, Wrong registration-15.0 %, Double registration-11.6 %, Inappropriate container-5.5 %, Sample spillage-3.9 %. Conclusion: The overall percentage of rejection in our hematology laboratory is 0.3 % and insufficient sample is the most common cause for rejection. Adequate training, regular maintenance of a record of errors and periodic auditing will result in effective reduction of such errors and hence improvement in the overall performance of laboratory works.