Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: in vitro characterization of agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid (LY404039)

Group II metabotropic glutamate (mGlu) receptor agonists, including (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate (LY354740) and (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), have demonstrated efficacy in animal models of anxiety and schizophrenia, and LY354740 decreased anxiety in human subjects. Herein, we report the in vitro pharmacological profile and pharmacokinetic properties of another potent, selective, and structurally novel mGlu2/3 receptor agonist, (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039) and provide comparisons with LY354740. Similar to LY354740, LY404039 is a nanomolar potent agonist at recombinant human mGlu2 and mGlu3 receptors (K(i) = 149 and 92, respectively) and in rat neurons expressing native mGlu2/3 receptors (Ki = 88). LY404039 is highly selective for mGlu2/3 receptors, showing more than 100-fold selectivity for these receptors, versus ionotropic glutamate receptors, glutamate transporters, and other receptors targeted by known anxiolytic and antipsychotic medications. Functionally, LY404039 potently inhibited forskolin-stimulated cAMP formation in cells expressing human mGlu2 and mGlu3 receptors. Electrophysiological studies indicated that LY404039 suppressed electrically evoked excitatory activity in the striatum, and serotonin-induced l-glutamate release in the prefrontal cortex; effects reversed by LY341495. These characteristics suggest LY404039 modulates glutamatergic activity in limbic and forebrain areas relevant to psychiatric disorders; and that, similar to LY354740, it works through a mechanism that may be devoid of negative side effects associated with current antipsychotics and anxiolytics. Interestingly, despite the slightly lower potency (approximately 2-5-fold) of LY404039 versus LY354740 in binding, functional, and electrophysiological assays, LY404039 demonstrated higher plasma exposure and better oral bioavailability in pharmacokinetic experiments. Collectively, the current data indicate that LY404039 may be valuable in the treatment of neuropsychiatric disorders, including anxiety and psychosis.     

Sexual assessment: research and clinical

It has been well documented that most patients do not volunteer information about sexual problems, and that health care providers should incorporate at least a brief sexual assessment into routine health histories and medical evaluations. While not every nurse can be a sexual counselor, listening to concerns of patient and family, presenting factual information in a nonthreatening manner, managing noncomplex disease and treatment related symptoms, and providing appropriate referrals can be easily incorporated into routine care.     

Patterns of lumbar region movement during trunk lateral bending in 2 subgroups of people with low back pain

BACKGROUND AND PURPOSE: The movement system impairment (MSI) system is one proposed system for classifying low back pain (LBP) problems. Prior clinical data and observations for the MSI system suggest that different LBP subgroups demonstrate different patterns of movement during clinical tests, such as trunk lateral bending (TLB). The purpose of this study, therefore, was to examine the validity of the observation that lumbar region (LR) movement patterns during TLB are different between 2 subgroups of people with LBP: lumbar rotation with extension (Rotation With Extension) and lumbar rotation (Rotation). SUBJECTS: Participants were 44 people (28 men and 16 women; age [X+/-SD], 28.5+/-8.4 years) with chronic or recurrent LBP. METHODS: Each participant's LBP problem was classified with the MSI system. Kinematic variables were measured, and LBP symptoms were recorded during the TLB test. RESULTS: People in the 2 LBP subgroups demonstrated different patterns of LR movement during TLB. People in the Rotation With Extension subgroup displayed an asymmetric (right versus left) pattern of LR movement across the TLB movement, whereas people in the Rotation subgroup displayed a symmetric pattern of LR movement. Equal proportions of people in the 2 subgroups reported an increase in symptoms with the TLB test. DISCUSSION AND CONCLUSION: The patterns of LR movement across the TLB movement were different in 2 subgroups of people with LBP. The difference in the LR movement patterns between subgroups may be an important factor to consider in specifying the details of the interventions for these 2 LBP problems.     

Mapping placement educators’ conceptions of teaching

Objectives

This study sought to better understand the complexities of the placement learning environment and its possible influence on students’ learning development. Specifically, the study maps placement educators’ perceived conceptions of teaching and teaching in practice.

Design and participants

All placement educators across Wales (n = 266) were invited to complete a demographic questionnaire, the Lecturers’ Conception of Teaching and Learning questionnaire, and the Trainer Type Inventory via an anonymous postal route.

Results

Responses from 141 placement educators enabled the respondents’ inventory scores to be mapped across clinical disciplines, motivation for engaging with placement education and role perception. The results suggest that within a highly motivating and pastoral-care aware environment, undergraduate physiotherapy students are experiencing placement education that is predominantly underpinned by a knowledge transmission conception of teaching.

Conclusion

These are changing times for placement education development and it is important for those involved in education to work together, within the placement and academic learning environments, to articulate and contribute to a common learning goal for undergraduate students.     

Current assessments of quality and safety education in nursing

Concerns about the quality and safety of health care have changed practice expectations and created a mandate for change in the preparation of health care professionals. The Quality and Safety Education for Nurses project team conducted a survey to assess current levels of integration of quality and safety content in pre-licensure nursing curricula. Views of 195 nursing program leaders are presented, including information about satisfaction with faculty expertise and student competency development related to 6 domains that define quality and safety content: patient-centered care, teamwork and collaboration, evidence-based practice, quality improvement, safety, and informatics. With competency definitions as the sole reference point, survey respondents indicated that quality and safety content was embedded in current curricula, and they were generally satisfied that students were developing the desired competencies. These data are contrasted with work reported elsewhere in this issue of Nursing Outlook and readers are invited to consider a variety of interpretations of the differences.     

Studying sex and gender differences in pain and analgesia: a consensus report

In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?"     

Activation of the cortical pain network by soft tactile stimulation after injection of sumatriptan

The anti-migraine drug sumatriptan often induces unpleasant somatosensory side effects, including a dislike of being touched. With a double-blind cross-over design, we studied the effects of sumatriptan and saline on perception (visual analogue scale) and cortical processing (functional magnetic resonance imaging) of tactile stimulation in healthy subjects. Soft brush stroking on the calf (n=6) was less pleasant (p<0.04) and evoked less activation of posterior insular cortex in the sumatriptan compared to the saline condition. Soft brushing activated pain processing regions (anterior insular, lateral orbitofrontal, and anterior cingulate cortices, and medial thalamus) only in the sumatriptan condition, whereas activation of somatosensory cortices was similar in both conditions. Soft brush stroking on the palm (n=6) was equally pleasant in both conditions. One possible mechanism for the activation of pain processing regions by brush stroking is sensitization of nociceptors by sumatriptan. Another possibility is inhibition of a recently discovered system of low-threshold unmyelinated tactile (CT) afferents that are present in hairy skin only, project to posterior insular cortex, and serve affective aspects of tactile sensation. An inhibition of impulse transmission in the CT system by sumatriptan could disinhibit nociceptive signalling and make light touch less pleasant. This latter alternative is consistent with the observed reduction in posterior insular cortex activation and the selective effects of stimulation on hairy compared to glabrous skin, which are not explained by the nociceptor sensitization account.     

Supplemental nurse staffing in hospitals and quality of care

OBJECTIVE: To promote evidence-based decision making regarding hospital staffing, the authors examined the characteristics of supplemental nurses, as well as the relationship of supplemental staff to nurse outcomes and adverse events. BACKGROUND: The use of supplemental nurses to bolster permanent nursing staff in hospitals is widespread but controversial. Quality concerns have been raised regarding the use of supplemental staff. METHODS: Data from the 2000 National Sample Survey of Registered Nurses were used to determine whether the qualifications of supplemental nurses working in hospitals differed from permanent staff nurses. Data from Pennsylvania nurse surveys were analyzed to examine whether nurse outcomes and adverse events differed in hospitals with varying proportions of nonpermanent nurses. RESULTS: Temporary nurses have qualifications similar to permanent staff nurses. Deficits in patient care environments in hospitals employing more temporary nurses explain the association between poorer quality and temporary nurses. CONCLUSION: Negative perceptions of temporary nurses may be unfounded.