"It Makes You Feel Good to Help!": An Exploratory Study of the Experience of Peer Mentoring in Long-Term Care.

Social isolation and loneliness in long-term care settings are a growing concern. Drawing on concepts of social citizenship, we developed a peer mentoring program in which resident mentors and volunteers formed a team, met weekly for training, and paired up to visit isolated residents. In this article, we explore the experiences of the resident mentors. As part of a larger mixed-methods study conducted in 10 sites in Canada, we interviewed mentors (n = 48) and analysed data using inductive thematic analysis. We identified three inter-related themes: Helping others, helping ourselves described the personal benefits experienced through adopting a helping role; Building a bigger social world encapsulated new connections with those visited, and; Facing challenges, learning together described how mentors dealt with challenges as a team. Our findings suggest that a structured approach to mentoring benefits residents and helps them feel confident taking on a role supporting their isolated peers.

The Impact of Peer Mentoring on Loneliness, Depression, and Social Engagement in Long-Term Care.

Loneliness, depression, and social isolation are common among people living in long-term care homes, despite the activities provided. We examined the impact of a new peer mentoring program called Java Mentorship on mentees' loneliness, depression, and social engagement, and described their perceptions of the visits. We conducted a mixed-methods approach in 10 homes in Ontario, Canada, and enrolled residents as mentees (n = 74). We used quantitative surveys and qualitative interviews to understand their experience. After 6 months, mentees (n = 43) showed a 30% reduction in depression (p = .02, d = .76), a 12% reduction in loneliness (p = .02, d = .76), and a 60% increase in the number of monthly programs attended (p = .01, d = .37), with small-to-medium effect sizes. The analysis of mentee's interviews revealed positive perceptions. This program offers an innovative, nonpharmacological alternative to the treatment of loneliness and depression.

'It makes life worthwhile!' Peer mentoring in long-term care-a feasibility study.

Objectives: Loneliness and depression are of increasing concern in long-term care homes made more urgent by viral outbreak isolation protocols. An innovative program called Java Mentorship was developed that engaged community volunteers and resident volunteers (mentors) as a team. The team met weekly, received education, and provided visits and guidance in pairs to socially disengaged residents (mentees). The purpose of this study was to assess the feasibility of conducting a larger study.Method: We conducted a mixed-methods pre-post study to evaluate the program. We collected feasibility data associated with the program implementation, including assessment of the sample and ability to recruit; procedures for data collection; retention, program adherence and acceptability; and residents' responses including loneliness, depression, purpose in life, social identity and sense of belonging outcomes. We enrolled community mentors (n = 65), resident mentors (n = 48) staff facilitators (n = 24) and mentees (n = 74) in 10 Canadian sites.Results: Most feasibility objectives were met, and adherence and acceptability were high. Some resource challenges and low retention rates among resident mentors were noted. We found a 29% reduction in depression scores (p = .048; d = .30) and 15% reduction in loneliness scores (p = .014; d = .23). Purpose in life, social identity and sense of belonging were unchanged. Interviews among participants indicated high acceptability and positive perceptions of the program.Conclusion: The study findings reveal a potential role for mentorship as a viable approach to reducing loneliness and depression in long-term care settings and lay the groundwork for future research.

Use of fall risk increasing drugs in residents of retirement villages: a pilot study of long term care and retirement home residents in Ontario, Canada.

BACKGROUND: Falls continue to be a problem for older people in long-term care (LTC) and retirement home (RH) settings and are associated with significant morbidity and health care use. Fall-risk increasing drugs (FRIDs) are known to increase fall risk and represent modifiable risk factors. There are limited data regarding the use of FRIDs in contemporary LTC and RH settings, and it has not been well documented to what extent medication regimens are reviewed and modified for those who have sustained falls. The objective of this study is to characterize medication related fall risk factors in LTC and RH residents and on-going use of medications known to increase fall risk. METHODS: Retrospective chart review of residents aged >65 who sustained one or more falls living in LTC or RH settings. RESULTS: 105 residents who fell one or more times during 2009-2010 were identified with a mean age of 89 years, a mean of nine scheduled medications and seven diagnoses, and 83% were women. Residents in LTC were ostensibly at higher risk for falls relative to those in RH settings as suggested by higher proportion of residents with multiple falls, multiple comorbidities, comorbidities that increase fall risk and visual impairment. Post fall injuries were sustained by 42% of residents, and residents in RH sustained more injuries relative to LTC residents (47 vs 34%). Use of FRIDs such as benzodiazepines, antipsychotic, antidepressant and various antihypertensive drugs was common in the present sample. No medication regimen changes were noted in the 6-month post fall period. CONCLUSIONS: The present study documented common use FRIDs by LTC and RH residents with multiple falls. These potentially modifiable falls risk factors are not being adequately addressed in contemporary practice, demonstrating that there is much room for improvement with regards to the safe and appropriate use of medications in LTC and RH residents.

HEALTH SELECTION THEORY: AN EXPLANATION FOR THE PARADOX BETWEEN PERCEIVED MALE WELL-BEING AND MORTALITY.

Paradoxically, men report better health and quality of life than women, but men experience higher mortality rates than women at most ages. One conclusion from these findings is that men have been selected to disregard signs of ill health, or even to deceive themselves about their health, to their detriment because presenting themselves as healthy has fitness benefits. We hypothesize that men have been sexually selected to present themselves to women as healthy but that the cost of not attending to their minor health problems results in earlier mortality than women. We present a review of the human and primate literature that supports health selection theory, the hypothesis that females have preferentially selected males who present themselves as healthy.

Helping pharmacists to reduce fall risk in long-term care: A clinical tool to facilitate the medication review process.

BACKGROUND: One-third to one-half of adults older than 65 fall at least once per year. Fall prevention through medication management requires little effort and has consistently been shown to reduce risk of falls. The objective of this study was to further develop and perform preliminary pilot testing of an algorithm designed to assist consultant pharmacists in systematically identifying medications that might be modifiable, in order to reduce the risk of falls in older adults. We hypothesized that algorithm use would increase the number of fall-related medication change recommendations made to physicians. METHODS: Four consultant pharmacists were trained to use the algorithm during their routine medication reviews over a 3-week period. An informal survey was administered at the end of the study period to assess the algorithm. RESULTS: Overall, 51% of residents of long-term facilities had 1 or more recommendations for medication changes related to reducing fall risk (range 0-3 recommendations per resident), with an average 0.675 recommendations made per resident. There were more recommendations for men compared with women and for residents receiving more medications, but the number of recommendations did not correspond with age. All 4 pharmacists agreed that the algorithm was useful and worthwhile. DISCUSSION: The absolute 20% increase in recommendations related to falls supports the study hypothesis. Time was cited as a barrier to using the algorithm, but this should decrease with continued use of this tool. CONCLUSION: This preliminary study furthered the development of and confirmed the possible utility and acceptability of a fall risk-reducing algorithm that may be used in practice.

Ultra-High-Throughput Screening of Natural Product Extracts to Identify Proapoptotic Inhibitors of Bcl-2 Family Proteins.

Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). Although several isoform-selective inhibitors have been developed using structure-based design or high-throughput screening (HTS) of synthetic chemical libraries, no large-scale screen of natural product collections has been reported. A competitive displacement fluorescence polarization (FP) screen of nearly 150,000 natural product extracts was conducted against all six antiapoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands that mimic functionally relevant PPIs. The screens were conducted in 1536-well format and displayed satisfactory overall HTS statistics, with Z'-factor values ranging from 0.72 to 0.83 and a hit confirmation rate between 16% and 64%. Confirmed active extracts were orthogonally tested in a luminescent assay for caspase-3/7 activation in tumor cells. Active extracts were resupplied, and effort toward the isolation of pure active components was initiated through iterative bioassay-guided fractionation. Several previously described altertoxins were isolated from a microbial source, and the pure compounds demonstrate activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate the feasibility of ultra-high-throughput screening using natural product sources and highlight some of the challenges associated with this approach.

Psychotropic and cognitive-enhancing medication use and its documentation in contemporary long-term care practice.

BACKGROUND: In long-term care (LTC) settings, use of psychotropic medications to manage behavioral and psychological symptoms of dementia and use of cognitive enhancers are commonplace. It is important that these medications are properly used to ensure resident well-being, and thus, it is paramount to understand use of these medications in contemporary practice to develop appropriate quality improvement initiatives. OBJECTIVE: To characterize psychotropic and cognition-enhancing medication use LTC residents and current trends in documentation. METHODS: Cross-sectional chart review of residents aged >65 years with dementia receiving psychotropic medications and/or cognitive enhancers. RESULTS: From 180 residents, 84 (82% female) met inclusion criteria (average age 86 years). The prevalence of psychotropic medication use was as follows: cognitive enhancers, 71%; antidepressants, 98%; antipsychotics, 61%; sedative hypnotics, 23%. Quetiapine was the most commonly used antipsychotic (48%), followed by risperidone (28%) and olanzapine (15%), all of which were dosed within accepted guidelines. The duration of therapy ranged from 2 to 5 years for antipsychotic medications and 1» to 3 years for antidepressants. Documentation documentation rates were hightest for psychotropics versus cognitive enhancers. There was no documentation of attempts to lower doses or discontinue psychotropic medications or cognitive enhancers. CONCLUSIONS: Many, but not all psychotropics used were acceptable choices. The duration of therapy appears to be excessive for antipsychotic medications. Documentation of ongoing need for medications varied and could be improved on to better assess residents' medication regimens. Further research will inform efforts to enhance the care of these residents.

Social identification moderates cognitive health and well-being following story- and song-based reminiscence.

OBJECTIVES: Reminiscence is a popular intervention for seniors, but, with mixed evidence supporting its efficacy, questions have been raised about the mechanisms underlying improvement. The present paper addresses this question by investigating the degree to which health effects depend on the development of a shared sense of group identification. This is examined in the context of traditional story-based reminiscence as well as novel forms of song-based reminiscence. METHOD: As the focus of a manualized intervention, 40 participants were randomly assigned to secular song (n=13), religious song (n=13), or standard story reminiscence (n=14) groups. These were run over six weeks with cognitive performance, anxiety, and life satisfaction measured before and after the intervention. Measures of group fit were included to examine whether social identification contributed to outcomes. RESULTS: No evidence of change emerged over time as a function of intervention form alone, but analysis of identification data revealed significant interactions with the type of reminiscence group. Specifically, initial fit with the story reminiscence group was associated with enhanced cognitive outcomes and greater life satisfaction, while fit with the religious song reminiscence group was associated with greater life satisfaction and less anxiety. CONCLUSION: These findings show that group identification is a key moderator through which reminiscence promotes health outcomes. Implications for theory and practice highlight an inherent limitation in randomized controlled trials insofar as they may compromise participants' group identification.

Collectivism/individualism and its relationship to behavioral and physiological immunity.

The interaction between the behavioral and physiological immune systems provides fertile ground for research. Here, we examine the interactions between fear of disease, collectivism/individualism, disgust, visual perception and salivary IgA. First, we parsed collectivism/individualism into ancestry and psychological processes and examined their relationships to fear of disease. Both ancestral and psychological collectivists scored higher on a test of hypochondria than individualists. Additionally, in two studies we exposed participants to slides of diseased, injured or healthy individuals. Diseased and injured stimuli were rated as equally disgusting, while diseased stimuli were rated as more disgusting than healthy stimuli. We measured salivary IgA in participants before and after they viewed the stimuli. Participants provided information on their ancestral collectivism or individualism. Salivary IgA levels increased after participants viewed images of diseased or injured individuals. Participants with collectivist ancestry tended to react to the diseased and injured images with an increase in IgA, while levels of IgA remained the same or decreased in individualists in one study but we failed to replicate the effect in the second study. An increased salivary IgA response to potentially diseased individuals is adaptive, because salivary IgA plays an important role in protecting individuals from contracting an infection. The response may be related to increased preoccupation with disease states.

New diarylheptanoids and a hydroxylated ottelione from Ottelia alismoides.

Ten new diarylheptanoids (2, 3, 4, 5a-d, 6, 7, and 8) have been isolated from an extract of Ottelia alismoides. The structures of these previously unknown metabolites were determined by NMR spectroscopic analysis. A previously unknown, hydroxylated analog of the known otteliones A and B (1a and 1b)--namely, 3a-hydroxyottelione (13)--was also isolated. The 1H NMR analysis of the Mosher esters of alcohols derived from otteliones A and B (S-17/R-17 and S-20/R-20) are also reported.

Polycationic calixarene PTX013, a potent cytotoxic agent against tumors and drug resistant cancer.

Previously, we reported on the anti-tumor activities of two designed calix[4]arene-based topomimetics (PTX008 and PTX009) of the amphipathic, angiostatic peptide Anginex. Here, we chemically modified the hydrophobic and hydrophilic faces of PTX008 and PTX009, and discovered new calixarene compounds that are more potent, cytotoxic anti-tumor agents. One of them, PTX013, is particularly effective at inhibiting the growth of several human cancer cell lines, as well as drug resistant cancer cells. Mechanistically, PTX013 induces cell cycle arrest in sub-G1 and G0/G1 phases of e.g. SQ20B cells, a radio-resistant human head and neck carcinoma model. In the syngeneic B16F10 melanoma tumor mouse model, PTX013 (0.5 mg/Kg) inhibits tumor growth by about 50-fold better than parent PTX008. A preliminary pharmacodynamics study strongly suggests that PTX013 exhibits good in vivo exposure and a relatively long half-life. Overall, this research contributes to the discovery of novel therapeutics as potentially useful agents against cancer in the clinic.

Case study of empirical and computational chemical shift analyses: reassignment of the relative configuration of phomopsichalasin to that of diaporthichalasin.

Phomopsichalasin was isolated and assigned structure 1 over 15 years ago. Analysis of its proton NMR data led us to hypothesize that not all aspects of the relative configuration of this structure were correct. We have used both empirical and computational methods to propose an alternative structure. Diaporthichalasin was reported several years ago, and its structure was assigned as 7, a diastereomer of structure 1, and confirmed by a single-crystal X-ray study. We have shown that diaporthichalasin and phomopsichalasin are identical; that is, both have structure 7. Additional aspects of NMR interpretation that provide guidance for avoiding some of the pitfalls that can lead to incorrect structure assignments are discussed. These recommendations/reminders include (i) the use of complementary solvents for acquiring NMR data that break accidental chemical shift degeneracy, (ii) the importance of assigning coupling constants as extensively as possible, and (iii) exercising caution when interpreting correlations in 2D spectra where overlapping resonances are involved.

Women's sexuality, well-being, and the menstrual cycle: methodological issues and their interrelationships.

Although many studies report that women's sexual behavior varies across their menstrual cycles, the research findings remain inconsistent. In this study, we addressed two methodological issues in research on the menstrual cycle: how ovulation is measured/inferred and whether data using menstrual cycles or participants' scores averaged across cycles as units of analysis yield similar results. We also employed an abstinent comparison group in addition to examining how emotional well-being was related to libido and sexual behavior through factor and regression analysis. Data were obtained from 97 participants. There were no significant differences in the results of analyses performed using cycles with known LH surges to determine ovulation versus cycles based on backward counts. However, we concluded that statistical power might be compromised when the known timing of ovulation was less accurate. Likewise, we found few overall differences in the results when we analyzed data using cycles with known LH surges compared to participants' averaged data across cycles. Women, including those in the abstinent group, reported increased sexual behavior prior to ovulation. Allosexual behavior was positively related to libido, and negatively related to positive and "premenstrual" emotional factors. Autosexual behavior was predicted by libido and an energetic/creative emotional factor. Our findings support hypotheses that women's sexual behavior is related to both mating and pair-bond formation.

Total synthesis of clathculins A and B.

Clathculins A and B represent a new class of vic-diamine alkaloids containing a PA2 unit as the basic structure. We report the first total syntheses of 1 and 2, which confirm the assigned structure of each. Dependence of their NMR spectroscopic behavior as a function of protonation state has been observed.

Well-being, sleep, exercise patterns, and the menstrual cycle: a comparison of natural hormones, oral contraceptives and depo-provera.

Overall well-being, sleep and exercise patterns were investigated in women between the ages of 18 and 36 years with natural hormone profiles (n = 12), and women using oral contraceptives (n = 12) or Depo-Provera (n = 12) from January 18, 2005 to December 7, 2005. Daily questionnaires on the above variables were obtained across 3 menstrual cycles (108 cycles). Women using hormonal contraception reported more overall negative well-being than women with natural hormone profiles (p = .038). Positive well-being at mid-cycle was positively correlated with increased sleep by the natural hormone (p < .05) and oral contraception groups (p < .05) but not by the Depo-Provera group. Women with natural hormone profiles walked more when they reported decreased well-being. Our findings indicate that the use of Depo-Provera interferes with the natural relations between sleep, cycle phase and well-being.

The menstrual cycle and sexual behavior: relationship to eating, exercise, sleep, and health patterns.

Patterns of eating, exercise, sleep, and health were investigated across 180 menstrual cycles of 89 women who engaged in sex with a male (n = 45; cycles = 85), a female (n = 21; cycles = 37), or abstained from sex (n = 33; cycles = 58) from January 2005 to December 2007 (10 contributed to 2 groups). Cycles were divided into 5 phases based on their luteinizing hormone surges. Daily questionnaires and saliva for IgA and cortisol analyses were obtained. Women indicated that they ate more (p < .008) and did not sleep as well (p = .02) during their luteal and premenstrual phases. Participants were less likely to experience food cravings and did not satisfy their cravings when they were ovulatory (p < .001). Additionally, a greater proportion of lesbians skipped breakfast (p = .01) and exercised less than heterosexuals (p = .05). Sexually active women had lower cortisol and IgA levels than abstinent women (p = .02). Our study discovered, and confirmed, systematic differences in eating, sleeping, and health patterns across women's menstrual cycles.

Production of a recombinant antibody fragment in whole insect larvae.

Infection of insect cells with baculovirus expression constructs is commonly used to produce recombinant proteins that require post-translational modifications for their activity, such as mammalian proteins. However, technical restraints limit the capacity of insect cell-based culture systems to be scaled up to produce the large amounts of recombinant protein required for human pharmaceuticals. In this study, we designed an automated insect rearing system and whole insect baculovirus expression system (PERLXpress) for the expression and purification of recombinant proteins on a large scale. As a test model, we produced a recombinant mouse anti-botulinum antibody fragment (Fab) in Trichoplusia ni larvae. A recombinant baculovirus co-expressing the Fab heavy and light chains together with N-terminal sequences from the silkworm hormone bombyxin, to direct proteins into the secretory pathway, was constructed. Fifth instar larvae were reared and infected orally with recombinant (pre- occluded) baculovirus using the automated system and harvested approximately after 4 days. The total yield of recombinant Fab was 1.1 g/kg of larvae, resulting in 127 mg of pure Fab in one production run. The Fab was purified to homogeneity using immobilized metal affinity chromatography, gel filtration, and anion exchange chromatography. The identity of the purified protein was verified by Western blots and size-exclusion chromatography. Purified recombinant Fab was used to detect botulinum toxin in ELISA experiments, demonstrating that the heavy and light chains were properly assembled and folded into functional heterodimers. We believe that this is the first demonstration of the expression of a recombinant antibody in whole insect larvae. Our results demonstrate that a baculovirus-whole larvae expression system can be used to express functionally active recombinant Fab fragments. As the PERLXpress system is an automated and linearly scalable technology, it represents an attractive alternative to insect cell culture for the production of large amounts of human pharmaceuticals.

Using hand performance measures to predict handedness.

Handedness is defined by the individual's preference to use one hand predominately for unimanual tasks and the ability to perform these tasks more efficiently with one hand (Corey, Hurley, & Foundas, 2001). It is important to use performance variables to measure handedness because they are more objective than traditional hand preference questionnaires (Bryden, Pryde, & Roy, 2000a). The current study develops a predictive model of handedness as measured by the Waterloo Handedness Questionnaire (WHQ) using several performance indicators of handedness. A total of 120 individuals (60 right-handers and 60 left-handers) were asked to complete four performance-based tasks: the Grooved Pegboard (GP), the Annett pegboard (AP), finger tapping (FT), and grip strength (GS) as well as an observational measure of preference, the Wathand Box Test (WBT). Backward linear regression analysis showed that the Wathand Box measure and the laterality quotients for several performance measures (GP place, AP, and FT) combined to act as the most accurate predictors of hand preference. The predictive model of handedness developed is as follows: WHQ = -2.760- - 0.667(GP place) + 0.809(FT) + 0.234(WBT) - 0.748(AP) with an explained variance of 0.836. These results illustrate, as Corey et al. (2001) suggested, that the best predictive model of handedness combines preference measures and several performance measures that tap into different elements of motor performance. By developing this model, it is possible to get an accurate measure of handedness using objective measures.