Molecular mechanism of interspecies differences in the binding affinity of TD139 to Galectin-3.

Galectin-3 (Gal-3), a ß-galactoside-binding lectin, has been implicated in a plethora of pathological disorders including fibrosis, inflammation, cancer and metabolic diseases. TD139-a thio-digalactoside inhibitor developed by Galecto Biotech as a potential therapeutic for idiopathic pulmonary fibrosis-is the most advanced small-molecule Gal-3 inhibitor in clinical studies. It binds to human Gal-3 with high affinity but has lower affinity towards mouse and rat homologs, which is also manifested in the differential inhibition of Gal-3 function. Using biophysical methods and high-resolution X-ray co-crystal structures of TD139 and Gal-3 proteins, we demonstrate that a single amino acid change corresponding to A146 in human Gal-3 is sufficient for the observed reduction in the binding affinity of TD139 in rodents. Site-directed mutagenesis of A146V (in human Gal-3) and V160A (in mouse Gal-3) was sufficient to interchange the affinities, mainly by affecting the off rates of the inhibitor binding. In addition, molecular dynamics simulations of both wild-type and mutant structures revealed the sustained favorable noncovalent interactions between the fluorophenyl ring and the active site A146 (human Gal-3 and mouse V160A) that corroborate the finding from biophysical studies. Current findings have ramifications in the context of optimization of drug candidates against Gal-3.

SAFE Medication Management for Patients With Physical Impairments of Stroke, Part Two.

PURPOSE: Part one of this series addressed impairments of stroke affecting motor skills. This second article focuses on the sensory impairments of stroke as they affect medication management: vision, hearing, memory and thinking, communication, and emotional disturbances. DESIGN: Each impairment is discussed, and possible interventions are proposed. Every patient is an individual and requires variable care plans. METHOD: Interventions and strategies, such as tools for assessment, practice tips, and assistive devices, aid patients, families, and their caregivers in practicing safe medication management. FINDINGS: Development of a comprehensive care plan will assist the patient to return as close to previous capabilities as possible. Patient outcomes and successes are variable. CONCLUSIONS AND CLINICAL RELEVANCE: The rehabilitation nurse uses observation, skills, and experience to assess stroke patients' needs and develop strategies to assist the patient in managing their medications. Involving patient, family, and caregivers in the teaching of SAFE (Systematic, Accurate, Functional, Effective) medication management increases safety, decreases the number of adverse drug events, and prevents hospitalizations.

Development of a RapidFire mass spectrometry assay and a fluorescence assay for the discovery of kynurenine aminotransferase II inhibitors to treat central nervous system disorders.

Kynurenine aminotransferases convert kynurenine to kynurenic acid and play an important role in the tryptophan degradation pathway. Kynurenic acid levels in brain have been hypothesized to be linked to a number of central nervous system (CNS) disorders. Kynurenine aminotransferase II (KATII) has proven to be a key modulator of kynurenic acid levels in brain and, thus, is an attractive target to treat CNS diseases. A sensitive, high-throughput, label-free RapidFire mass spectrometry assay has been developed for human KATII. Unlike other assays, this method is directly applicable to KATII enzymes from different animal species, which allows us to select proper animal model(s) to evaluate human KATII inhibitors. We also established a coupled fluorescence assay for human KATII. The short assay time and kinetic capability of the fluorescence assay provide a useful tool for orthogonal inhibitor validation and mechanistic studies.

SAFE Medication Management for Patients with Physical Impairments of Stroke, Part One.

PURPOSE: This article focuses on the extensive impairments of stroke and their influence on medication management. The impairments of motor skills due to paralysis-loss of mobility and balance, lack of hand-to-mouth coordination, and difficulty swallowing-are discussed. A future article will discuss sensory impairments of vision, hearing, cognition, comprehension, communication, and emotional disorders and how these impairments influence medication management. DESIGN: Each of the impairments are presented and discussed, and possible interventions are proposed. Every patient is an individual and requires variable care plans. METHOD: Intervention strategies that include tools for patient assessment, practice tips, and devices available to assist the patient and family in safe medication management are presented. FINDINGS: Patient outcomes and successes vary, but the strategies outlined will return the patient to as close to previous capabilities as possible. CONCLUSION AND CLINICAL RELEVANCE: Teaching SAFE (Systematic, Accurate, Functional, Effective) medication management to the patient, family, and caregivers will increase medication safety and decrease the number of adverse effects. The rehabilitation nurse is charged with evaluating the patients' needs and developing strategies to assist them to manage their medications.

Teaching adults SAFE medication management.

One in nine visits to the emergency department is the result of a drug-related adverse event and is possibly preventable (Zed et al., 2008). The rehabilitation nurse has the opportunity to teach adults a comprehensive medication management plan that will help reduce medication errors. Most patients have minimal medication experience or instruction; this article documents the effectiveness of using a S = systematic, A = accurate, F = functional, and E = effective instructional methodology to help patients learn about their medications. The methodology helps rehabilitation nurses teach the average patient about handling, absorbing, and implementing the information. This article presents detailed instruction about the salient points of the SAFE instructional program. Several figures, a checklist, and pictures demonstrate the techniques utilized. Prevention of medication errors is emphasized throughout.

Conditional embryo relinquishment: choosing to relinquish embryos for family-building through a Christian embryo 'adoption' programme.

BACKGROUND: Currently, there is little evidence about conditional relinquishment of frozen embryos to others for family-building. This paper begins to address this gap by reporting findings from a study that investigated the experiences of couples who chose to relinquish their embryos conditionally through an embryo 'adoption' programme. METHODS: An exploratory qualitative study was conducted between September 2008 and December 2009. Participants were recruited from a Christian embryo 'adoption' programme in the USA. Forty-three people (18 couples and 7 wives) participated in in-depth email interviews. RESULTS: The data show that the following factors contributed to the participants choosing an embryo 'adoption' programme: how they conceptualized their embryos; dislike of alternative disposition options available; conceptions of their parental responsibility towards their embryo and a desire to have an 'open' relinquishment with (varying) degrees of information-sharing and contact arrangements between themselves and recipient couples. CONCLUSIONS: This study identifies a diversity of views on embryo relinquishment and some couples' wishes for elements of conditional relinquishment that are offered by embryo 'adoption' programmes. A range of disposition options should be available to enhance choice for those with unused embryos so that they can relinquish in ways that are both morally and practically acceptable to them. The current polarized debate concerning the language of embryo 'adoption' detracts attention from the practical considerations of formulating 'best practice' in this area. These considerations are better addressed by the use of less politically charged terminology such as 'conditional relinquishment'.

Relinquishing frozen embryos for conception by infertile couples.

This qualitative study sought to provide an in-depth understanding of the experiences of couples who have relinquished their stored frozen embryos to one or more infertile couples. All couples were recruited through a U.S. based not-for-profit, prolife, Christian "embryo adoption" agency. In-depth semistructured interviews were undertaken via e-mail. Implications for practice strategies, including effective ways for educating couples with surplus frozen embryos are offered.

Medication safety series: take charge!

Nurses have read the statistics on the numbers of prescription medications seniors take each day and the pitfalls and diverse problems that occur as a result. Various scenarios contribute to this problem: multiple healthcare providers prescribe medications; the use of over-the-counter products and herbs or alcohol cause medication interactions; and patients increase, decrease, skip, or repeat doses. When medications are not taken correctly, an increase in the number of physician or emergency department visits and hospitalizations results. Patients who come to a rehabilitation unit after joint replacement or hip-pinning surgery, stroke, or for treatment of other conditions may be prescribed medications that differ from the drugs they were taking at home. These patients and their families need to learn how to safely take their new medications. This presentation describes how five nurses developed a medication safety program consisting of four segments: Making Your Medication List; Talking to Your Healthcare Team About Your Medications; Safely Storing, Taking, and Destroying Your Medications; and Knowing the Difference Between Allergies, Side Effects, and Interactions. This article also describes the development of the script and PowerPoint program, lessons learned from the first presentation, and implications for rehabilitation nurses. The information presented in this series can help patients and families take charge of their medications. The team of community educators who wrote this article encourages the integration of this program into readers' local patient communities because standards of care and resources vary in the communities that nurses serve.

Family secrets and family functioning: the case of donor assistance.

The purpose of this study was to examine the relationship between adult offspring's perception of family functioning and of parental use of topic avoidance to maintain secrecy regarding the use of donor assistance to conceive. A cross-sectional design was used to study a convenience sample of 69 young adult donor offspring who completed a demographic questionnaire, a topic avoidance scale relative to each of their rearing parents, and the Beavers Self Report Family Instrument. Findings indicated that participants perceived both parents as avoiding the topic of donor assistance more than other topics, mothers as avoiding all topics less than fathers, and topic avoidance was negatively associated with family functioning. Mothers' general topic avoidance was the strongest predictor of family functioning. Parents' disclosing together was predictive of higher family functioning. Implications for practice and future research are suggested.

Topic avoidance and family functioning in families conceived with donor insemination.

BACKGROUND: While a move away from non-disclosure and secrecy toward more openness is demonstrated in the changing practices of donor insemination worldwide, scholars and practitioners continue to debate the effects of disclosure versus secrecy. This study examines if an association exists between adult donor offspring's perceptions of their parents' use of topic avoidance to maintain secrecy, and their perceptions of their family's functioning. METHODS: Using a cross-sectional design, a convenience sample of 69 young adult donor offspring completed a demographic questionnaire, a topic avoidance scale relative to each of their rearing parents, and the Beavers Self Report Family Instrument. RESULTS: There was a moderate significant inverse correlation between family functioning and topic avoidance in general, as well as for donor insemination-related topics, for both mothers (r = -0.55, r = -0.40, respectively, P