Comparison of three commercially available buffy coat pooling sets for the preparation of platelet concentrates

Background: A disposable set for platelet concentrate (PC) preparation by the buffy coat method allows pooling of buffy coats, centrifugation and cell separation with in-line leucocyte filtration. This study compares three commercially available pooling sets in combination with INTERCEPT pathogen inactivation (PI). Materials and methods: Sets for pooling of buffy coats were from Fresenius Kabi (FRE), Macopharma (MAC) and Terumo BCT (TER). Platelet yield, recovery and concentration were compared before and after PI (n = 20). Platelet quality was assessed by annexin V binding, P-selectin expression and PAC1 binding. Results: The TER pooling set had the highest platelet yield (539 044 x 10(11)) compared with MAC (453 +/- 077) and FRE (456 +/- 051) prior to PI. This was the result of a significantly higher platelet concentration in the TER storage bag (141 +/- 012 x 10(6)/L) compared with MAC (118 +/- 019) and FRE (128 +/- 015). However, the TER platelet content decreased by 156% after PI, yielding 455 +/- 047 x 10(11) platelets compared with smaller reductions at 95% for MAC (410 +/- 069) and 44% for FRE (436 +/- 052). None of the individual PC contained >10(6) leucocytes. The pH in TER PC was lower compared with MAC and FRE caused by a higher lactic acid production rate. Consequently, PAC1 binding after TRAP activation was lowest for TER PC on day 6. P-selectin and annexin V were not different between suppliers. Conclusion: This study demonstrates the added value of evaluating the entire component production process when introducing a new consumable. This study helped to inform a decision on what pooling set is ideally suited for routine implementation taking into account PI

Adoptee Information Seeking: Changes between Adolescence and Emerging Adulthood and the Impact of Adoption Communicative Openness

This dissertation examined changes in information seeking intentions and behaviors between adolescence and emerging adulthood for a group of adoptees who did not have direct contact with birth relatives in adolescence. Associations between information seeking in emerging adulthood and life cycle events typical of emerging adulthood, gender, and Adoption Communicative Openness were also examined. Data from 119 adoptees and their adoptive mothers were used from Waves 2 (1996-2000) and 3 (2005-2008) of the Minnesota-Texas Adoption Research Project (Grotevant & McRoy, 1998). Degree of information seeking between adolescence (Wave 2) and emerging adulthood (Wave 3) increased for the majority of adoptees (62.2%). Approximately 16% of adoptees experienced no change in information seeking and 22% of adoptees experienced a decrease in information seeking. Females were more likely to exhibit a greater increase in information seeking change between Waves 2 and 3 and information seeking at Wave 3 than males. Life cycle events typical of emerging adulthood including living out of adoptive parents’ home, being in a committed romantic relationship, and being a parent were not associated with information seeking in emerging adulthood. Number of life cycle events experienced also was not associated with information seeking in emerging adulthood. Adoption Communicative Openness was positively associated with degree of information seeking in emerging adulthood. Results suggest that adoptee information seeking is a dynamic process that takes place over several life stages and that open communication about adoption within the adoptive family supports adoptee information seeking

A Simple Tool to Predict End‐Stage Renal Disease within 1 Year in Elderly Adults with Advanced Chronic Kidney Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98206/1/jgs12223.pd

In vitro and in vivo activity of ML302F: a thioenolate inhibitor of VIM-subfamily metallo beta-lactamases

The thioenol ML302F was recently identified as an inhibitor of class B metallo-β-lactamases (MBLs). We assessed the activity of ML302F when combined with meropenem (MEM) against 31 carbapenem resistant Gram-negative clinical isolates. Minimum inhibitory concentrations of MEM : ML302F were determined at fixed ratios of 1 : 4 and 1 : 8 using strains producing variants of the clinically relevant VIM-like MBL. Toxicity and efficacy in vivo was assessed in a Galleria mellonella invertebrate model against strains producing VIM-1, VIM-2 and VIM-4 variants. At a fixed MEM : ML302F ratio of 1 : 8, 22/31 isolates were rendered either susceptible (MIC ≤ 2 mg L−1), or intermediate (MIC 4–8 mg L−1) to MEM. ML302F alone was not toxic at up to 80 mg kg−1 in G. mellonella and treatment with MEM 0.6 mg kg−1 : ML302F 4.8 mg kg−1 significantly improved the survival of infected larvae. As ML302F was able to successfully restore susceptibility to resistant strains both in vitro and in vivo it represents a structurally interesting inhibitor in the search for new MBL inhibitors

Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases

Respiratory tract disease can be associated with primary or secondary bacterial infections in dogs and cats and is a common reason for use and potential misuse, improper use, and overuse of antimicrobials. There is a lack of comprehensive treatment guidelines such as those that are available for human medicine. Accordingly, the International Society for Companion Animal Infectious Diseases convened a Working Group of clinical microbiologists, pharmacologists, and internists to share experiences, examine scientific data, review clinical trials, and develop these guidelines to assist veterinarians in making antimicrobial treatment choices for use in the management of bacterial respiratory diseases in dogs and cats.M.R. Lappin, J. Blondeau, D. Boothe, E.B. Breitschwerdt, L. Guardabassi, D.H. Lloyd, M.G. Papich, S.C. Rankin, J.E. Sykes, J. Turnidge, and J.S. Wees

Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1

In an effort to characterize the roles of each metal ion in metallo-β-lactamase NDM-1, heterodimetallic analogues (CoCo-, ZnCo-, and CoCd-) of the enzyme were generated and characterized. UV–vis, 1H NMR, EPR, and EXAFS spectroscopies were used to confirm the fidelity of the metal substitutions, including the presence of a homogeneous, heterodimetallic cluster, with a single-atom bridge. This marks the first preparation of a metallo-β-lactamase selectively substituted with a paramagnetic metal ion, Co(II), either in the Zn1 (CoCd-NDM-1) or in the Zn2 site (ZnCo-NDM-1), as well as both (CoCo-NDM-1). We then used these metal-substituted forms of the enzyme to probe the reaction mechanism, using steady-state and stopped-flow kinetics, stopped-flow fluorescence, and rapid-freeze-quench EPR. Both metal sites show significant effects on the kinetic constants, and both paramagnetic variants (CoCd- and ZnCo-NDM-1) showed significant structural changes on reaction with substrate. These changes are discussed in terms of a minimal kinetic mechanism that incorporates all of the data

Special Feature CKD as a Model for Improving Chronic Disease Care through Electronic Health Records

Abstract Electronic health records have the potential to improve the care of patients with chronic medical conditions. CKD provides a unique opportunity to show this potential: the disease is common in the United States, there is significant room to improve CKD detection and management, CKD and its related conditions are defined primarily by objective laboratory data, CKD care requires collaboration by a diverse team of health care professionals, and improved access to CKD-related data would enable identification of a group of patients at high risk for multiple adverse outcomes. However, to realize the potential for improvement in CKD-related care, electronic health records will need to provide optimal functionality for providers and patients and interoperability across multiple health care settings. The goal of the National Kidney Disease Education Program Health Information Technology Working Group is to enable and support the widespread interoperability of data related to kidney health among health care software applications to optimize CKD detection and management. Over the course of the last 2 years, group members met to identify general strategies for using electronic health records to improve care for patients with CKD. This paper discusses these strategies and provides general goals for appropriate incorporation of CKD-related data into electronic health records and corresponding design features that may facilitate (1) optimal care of individual patients with CKD through improved access to clinical information and decision support, (2) clinical quality improvement through enhanced population management capabilities, (3) CKD surveillance to improve public health through wider availability of population-level CKD data, and (4) research to improve CKD management practices through efficiencies in study recruitment and data collection. Although these strategies may be most effectively applied in the setting of CKD, because it is primarily defined by laboratory abnormalities and therefore, an ideal computable electronic health record phenotype, they may also apply to other chronic diseases

Designing Irreversible Inhibitors—Worth the Effort?

This is the peer-reviewed version of the following article: González-Bello, C. (2016). Designing Irreversible Inhibitors-Worth the Effort?. Chemmedchem, 11(1), 22-30, which has been published in final form at https://doi.org/10.1002/cmdc.201500469. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-ArchivingDespite the unquestionable success of numerous irreversible drugs that are currently in clinical use, such as acetylsalicylic acid (Aspirin) and penicillin, the number of such approved drugs is much lower than that of noncovalent drugs. Over the years, the potential off‐target effects of these types of compounds have been the primary concern that has hampered their development. However, their remarkable advantages over noncovalent drugs and a better analysis of the risks have decreased the widespread skepticism surrounding them. The design of irreversible inhibitors is a challenge, particularly considering that in some cases their efficacy is due to complex and unexpected mechanisms of action. In this review the main advantages of irreversible inhibition are summarized, and the complexity of certain covalent modification mechanisms is highlighted with selected examplesSpanish Ministry of Economy and Competitiveness. Grant Number: SAF2013-42899-R Xunta de Galicia. Grant Number: GRC2013-041 European Regional Development Fund (ERDF)S

Structural basis of metallo-β-lactamase, serine-β-lactamase and penicillin-binding protein inhibition by cyclic boronates

β-Lactamases enable resistance to almost all β-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as ‘transition state analogue’ inhibitors of nucleophilic serine enzymes, including serine-β-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent β-lactamases by a mechanism involving mimicking of the common tetrahedral intermediate. Cyclic boronates also potently inhibit the non-essential penicillin-binding protein PBP 5 by the same mechanism of action. The results open the way for development of dual action inhibitors effective against both serine- and metallo-β-lactamases, and which could also have antimicrobial activity through inhibition of PBPs

Predicting the risk of Chronic Kidney Disease in Men and Women in England and Wales: prospective derivation and external validation of the QKidney® Scores

<p>Abstract</p> <p>Background</p> <p>Chronic Kidney Disease is a major cause of morbidity and interventions now exist which can reduce risk. We sought to develop and validate two new risk algorithms (the QKidney^®Scores) for estimating (a) the individual 5 year risk of moderate-severe CKD and (b) the individual 5 year risk of developing End Stage Kidney Failure in a primary care population.</p> <p>Methods</p> <p>We conducted a prospective open cohort study using data from 368 QResearch^®general practices to develop the scores. We validated the scores using two separate sets of practices - 188 separate QResearch^®practices and 364 practices contributing to the THIN database.</p> <p>We studied 775,091 women and 799,658 men aged 35-74 years in the QResearch^®derivation cohort, who contributed 4,068,643 and 4,121,926 person-years of observation respectively.</p> <p>We had two main outcomes (a) moderate-severe CKD (defined as the first evidence of CKD based on the earliest of any of the following: kidney transplant; kidney dialysis; diagnosis of nephropathy; persistent proteinuria; or glomerular filtration rate of < 45 mL/min) and (b) End Stage Kidney Failure.</p> <p>We derived separate risk equations for men and women. We calculated measures of calibration and discrimination using the two separate validation cohorts.</p> <p>Results</p> <p>Our final model for moderate-severe CKD included: age, ethnicity, deprivation, smoking, BMI, systolic blood pressure, diabetes, rheumatoid arthritis, cardiovascular disease, treated hypertension, congestive cardiac failure; peripheral vascular disease, NSAID use and family history of kidney disease. In addition, it included SLE and kidney stones in women. The final model for End Stage Kidney Failure was similar except it did not include NSAID use.</p> <p>Each risk prediction algorithms performed well across all measures in both validation cohorts. For the THIN cohort, the model to predict moderate-severe CKD explained 56.38% of the total variation in women and 57.49% for men. The D statistic values were high with values of 2.33 for women and 2.38 for men. The ROC statistic was 0.875 for women and 0.876 for men.</p> <p>Conclusions</p> <p>These new algorithms have the potential to identify high risk patients who might benefit from more detailed assessment, closer monitoring or interventions to reduce their risk.</p